Department of Medicine Manipal College of Medical Sciences LUNG CANCER ALOK SINHA Department of Medicine Manipal College of Medical Sciences Pokhara, Nepal

Epidemiology One of commonest cause of cancer death Responsible for 25% of all cancer deaths More than 3 folds increase in cancer deaths since 1950

Male: female - 2: 1 Increasing in women 8% cancer deaths in men and 4% of cancer deaths in women Increasing in women increasing smoking

Predisposing Factors 1. Cigarette smoking Main predisposing factor 90% smoking-related Stopping smoking decreases the risk Passive smoking can also put people at risk High increases beyond 30 pack years 2. Exposure to Asbestos Asbestos exposure + cigarette smoking particularly harmful

can also increase risk 3. Other occupational exposures Arsenic preservation of wood added to a semiconductor like transistors in the tanning industry as a preservative anti-friction additive in ball bearings Chromium manufacture of stainless steel electroplating used as a yellow pigment Nickel & other heavy metals Used as alloys in many industries can also increase risk

4.Radiation exposure damages the DNA material within the cells and can also cause lung cancer 5.Radon (a radioactive gas) exposure can predispose to lung cancer. people living in areas with a high radon content are prone to increased incidences of a variety of cancers Levels high in basement

6. Pre existing non malignant lung diseases associated with increased lung cancer rates Tuberculosis Chronic obstructive pulmonary disease Idiopathic pulmonary fibrosis

Classification

1. Non small cell lung cancer (NSCLC) 75 -80% Squamous cell carcinoma Adenocarcinoma Alveolar cell carcinoma Large cell carcinoma 2. Small cell lung cancer (SCLC) 20 - 25% 3. Miscellaneous Carcinoid Sarcoma Unspecified lung cancer Oat Cell cancer

Non-small cell lung cancer (NSCLC) Squamous cell carcinoma Commonest histological type Centrally located Slow growing take several years to progress from a confined tumor into invasive cancer Causes pneumonia atelectasis etc Presents as a mass on CXR May cavitate and look like a lung abscess Response to chemotherapy is poor

Adenocarcinoma Not always smoking-related Are peripheral (NSCLC contd) Adenocarcinoma Not always smoking-related Are peripheral Can occur in scar tissue Can be a lung primary secondary from adenocarcinomas at other sites, especially if causing pleural infiltration Have a worse prognosis than squamous cell cancer in all stages

Alveolar cell carcinoma Rare Can cause copious sputum production (bronchorrhoea) Fluffy air space shadowing on CXR Large cell carcinoma an uncommon NSCLC similar to that of adenocarcinoma

Small cell lung cancer (SCLC or Oat cell ) STRONGLY associated with smoking More aggressive than NSCLC Presents as central lesion with hilar & mediastinal invasion along with regional adenopathy Rapidly growing -usually disseminated by the time of diagnosis (haematogenous spread) to Liver Bone & bone marrow Brain Adrenals, or elsewhere

Paraneoplastic syndromes like SIADH common (except PTH) Surgery usually not appropriate Chemo- and radiosensitive Untreated – rapidly progressive and has a median survival of 6 weeks

Common Symptoms Coughing – change in character in a smoker Weight loss Shortness of breath Chest pain : often ill-defined and aching Haemoptysis: sputum may be streaked with blood Non-specific symptoms: fever, weakness, lethargy Rarely difficulty in swallowing wheezing ? Monomorphic wheeze

Symptoms and signs Due to: Local tumour effects Metastatic tumour effects Paraneoplastic manifestations

local tumour effects Local involvement of the bronchus Mediastinal spread Compression of local nerves Superior vena cava syndrome Spread to the chest wall

Local involvement of the bronchus 1. Dry cough Purulent if there is secondary infection Change in the character of the 'regular' cough of a smoker 2. Haemoptysis (tumours arising in central bronchi) Repeated episodes of scanty haemoptysis blood-streaking of sputum in a smoker are highly suggestive of bronchial carcinoma and should always be investigated Occasionally massive: large vessels invaded, -may be fatal

3. Bronchial obstruction Complete obstruction Partial obstruction Partial – hyperinflation Complete – atelectasis dyspnoea

4. Pneumonia When the obstruction is insufficient to cause collapse Recurrent pneumonia in the same sight Delayed resolution of pneumonia 5. Lung abcess Due to obstruction Tumor undergoing necrosis 6. Wheeze/stridor due to airway obstruction Monophonic or unilateral wheeze failing to clear with coughing suggests presence of fixed bronchial obstruction

2. Mediastinal spread Oesophahgeal involvement causing dysphagia

3. Compression of local nerves Left recurrent laryngeal nerve palsy hoarse voice with 'bovine' cough Phrenic nerve paralysis unilateral diaphragmatic palsy shoulder pain dullness to percussion paradoxical movement of abdominal wall absent breath sounds at a lung base

4. Superior vena cava syndrome Bilateral engorgement of the jugular veins Distended veins over chest wall Oedema of Face Neck arms conjunctivae

superior vena cava syndrome

5. spread to the chest wall Pleural pain Pain due to intercostal nerve involvement Pancoast tumor (superior sulcus tumor, or tumor of the pulmonary apex) directly invade sympathetic chain Horner's syndrome (meiosis, ptosis, enopthalmos, anhidrosis) brachial plexus Cause weakness of small muscles of hand C5/6, T1 motor loss shoulder pain

Metastatic effects Local metastasis Blood born metastases

Local metastasis Cervical/supraclavicular lymphadenopathy common, present in 30% easy site for diagnostic biopsy

Blood born metastases C.N.S. involvement focal neurological defects epileptic seizures personality change Bone: pain & pathological fracture Skin nodules Liver: Jaundice Lassitude, anorexia and weight loss usually indicate the presence of metastatic spread

Non-metastatic extrapulmonary manifestations (Para neoplastic syndrome) Endocrine Inappropriate ADH secretion causing hyponatraemia (SIADH) Ectopic ACTH secretion – Cushings syndrome Parathyroid hormone (PTH)-related peptides - hypercalcaemia Carcinoid syndrome (Serotinin producing tumor causing diarrhoea brnchospasm) Gynaecomastia

C.N.S. Symptoms precede those of primary tumour itself Polyneuropathy Myelopathy Cerebellar degeneration Myasthenia (Lambert-Eaton syndrome) Limbic encephalitis Limbic system: collection of structures at the base of the brain responsible for emotions and memory Consists of Hippocampus, amygdala, anterior thalamic nuclei, limbic cortex Symptoms: memory loss, personality changes, anxiety or depression, neuropsychiatric disturbances, partial or generalized seizures, olfactory and gustatory hallucinations, sleep disturbances

Others Digital clubbing Hypertrophic pulmonary osteoarthropathy excessive proliferation of skin and bone at the distal parts of extremities, digital clubbing and periostosis of the tubular bones Nephrotic syndrome Polymyositis and dermatomyositis Eosinophilia

Differential diagnosis Large no of conditions having Cough & haemoptysis Clubbing & Gynaecomazia Pneumonic consolidation & collapse Features due to secondaries & paraneoplastic syndrome – may be the presenting symptoms

Investigations

1. CXR (PA and lateral) Normal CXR does not rule it out location of lesion pleural involvement, pleural effusion rib destruction intrathoracic metastases mediastinal lymphadenopathy Normal CXR does not rule it out

COMMON RADIOLOGICAL PRESENTATIONS OF BRONCHIAL CARCINOMA 1.Unilateral hilar enlargement 2. Parenchymal shadows 3. Lung, lobe or segmental collapse 4. Pleural effusion 5. Broadening of mediastinum, 6. enlarged cardiac shadow, 7. elevation of a hemidiaphragm 8. Rib destruction

2. Bronchoscopy For centrally located tumors Visualised directly using a flexible bronchoscope Bronchio Alveolar Lavage can be done - cytology Bronchial biopsies (and brush samples) can be taken for pathological examination direct assessment can be made of operability judged by the proximity of central tumours to the main carina

3. Percutaneous needle biopsy (under CT or ultrasound guidance) For peripheral lesions not accessible to the bronchoscope In patients not fit enough for bronchoscopy sputum cytology valuable diagnostic aid

5. Mediastinoscopy, thoracoscopy or thoracotomy 4. Pleural biopsy indicated in all patients with pleural effusions 5. Mediastinoscopy, thoracoscopy or thoracotomy required to obtain a definitive histological diagnosis

In patients with metastatic disease diagnosis confirmed by needle aspiration biopsy of affected lymph nodes skin lesions liver bone marrow

MANAGEMENT

T N M S t a g i n g

Extent of primary tumour (T) Regional lymph nodes (N) Distant metastasis (M)

TX T1 T2 T3 T0 Primary tumor can not be assesed No evidence of primary tumor T1 Tumor < 3 cm T2 Tumor > 3 cm more than 2 cm distal to carina T3 Tumor of any size Invading chest wall & diaphragm Causing atelectasis or pneumonia Less than 2 cm distal to carina T4 Tumor invading Mediastinum Vertebral bodies Malignant preural effusion

NX N0 N1 N2 N3 Lymph nodes can not be assessed No regional lymph node metastasis N1 Ipsilateral peribronchial or hilar lymph nodes N2 Ipsilateral mediastinal or subcarinal nodes N3 Contra lateral hilar, mediastinal or Supraclavicular nodes

Distant metastasis – M MX M0 M1 Can not be assessed No distant metastasis M1 Distant metastasis (including pleural effussion)

Stage groupings I T1 or 2 N - 0 M – 0 II T1, 2 or 3 N – 0 or 1 IIIA IIIB T4 N – 3 M - 0 IV M - 1

Surgical resection

In majority of cases (over 85%) surgery not possible due to Possible only in 15% In majority of cases (over 85%) surgery not possible due to extensive spread co-morbidity Only palliative surgery possible for them Best hope of long-term survival in slow growing tumors – squamous cell cancers limited to stage I or II

Distant metastasis (M1) CONTRAINDICATIONS Distant metastasis (M1) Invasion of central mediastinal structures including heart, great vessels, trachea and oesophagus (T4) Malignant pleural effusion Contralateral mediastinal nodes (N3) FEV1 < 0.8 litres (severe C.O.P.D.) Severe or unstable cardiac or other medical condition

5-year survival rates of Over 75% in stage I disease (N0, tumour confined within visceral pleura) 55% in stage II disease (ipsilateral peribronchial or hilar node involvement)

Radiotherapy Much less effective than surgery Radical radiotherapy offer long-term survival in selected patients with localised disease in whom surgery not possible Palliative radiotherapy For distressing complications such as superior vena caval obstruction recurrent haemoptysis Pain (due to chest wall invasion or skeletal metastatic deposits) Obstruction of the trachea and main bronchi

Chemotherapy Use ful in small-cell carcinoma Cytotoxic drugs + Radiotherapy increase the median survival of patients from 3 months to well over a year

Regular cycles of therapy given Combinations of commonly used drugs Cyclophosphamide Doxorubicin Vincristine Cisplatin Etoposide

Requires considerable medical skill and expertise Requires considerable medical skill and expertise. should only be given by teams of expert clinicians Chemotherapy given before surgery may increase survival in small cell carcinoma

Prognosis The overall prognosis : very poor 80% of patients dying within a year of diagnosis less than 6% of patients surviving 5 years after diagnosis Best prognosis is with well-differentiated squamous cell tumours which have not metastasised and are amenable to surgical treatment

Non–small cell lung cancer

Non–small cell lung cancer Non–small cell lung cancer. Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. pleural effusion was found to be malignant; therefore, the lesion is inoperable.

Non–small cell lung cancer. Left upper collapse secondary to endobronchial bronchogenic carcinoma.

Lung cancer, small cell. A large mass in left mid lung with an opacity extending to the upper lung.A small left pleural effusion is present, with blunting of the costophrenic recess.

cavitating right lower lobe squamous cell carcinoma