A move to equitable care

In Ethiopia “Approach to Diagnosis and Management”

Outline

• Epidemiology
• Risk Factors
• Screening
• Clinical Manifestation
• Evaluation of Lung cancer suspects
• Therapeutic options for Lung cancer

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Epidemiology

• WHO defines lung cancer as tumors arising from the respiratory epithelium (bronchi, bronchioles, and alveoli).

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• Lung cancer causes as many deaths as the next three leading causes of cancer deaths combined.

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• For many years, lung cancer was a relatively neglected disease, shrouded in pessimism and with little research funding.

Epidemiology

Source: GLOBOCAN 2020

Projected Number of New Cases for All Cancers Combined (Both Sexes Combined) in 2040 According to the 4-Tier Human Development Index

(HDI). Source: GLOBOCAN 2020

Global report estimates age adjusted Death Rate from Lung cancer to be 3.34 per 100,000 of population ranking Ethiopia #146 in the world

Risk Factors

• Cigarette smoking
• Ambient Air Pollution – Outdoor/Indoor
• Radon
• Asbestos
• Chronic Lung Diseases
• HIV

Risk Factors

• Smoking
• > 85% of lung cancers
• Polycyclic hydrocarbons
• One genetic mutation per 15 cig
• Life time risk (1% Vs 10-30%)
• Amount, Age at onset,
• Tar and nicotine content

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Smoking - Ethiopia

• Total smoking : 5.56% before 2014 while it’s 8.24% between 2014- 2017.

Global Burden of Disease Study 2019. The Lancet 2021

Ethiopia: Multi- sectoral and policy interventions for prevention of NCDIs �

SMOKE-FREE ENVIRONMENTS – HIGHEST ACHIEVING COUNTRIES, 2020

HEALTH WARNING LABELS – HIGHEST ACHIEVING COUNTRIES, 2020

Air Pollution

• A 40% increase in lung cancer risk was found in residents in the city with the highest concentration of fine particles.

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• Each 10 g/m3 increase in concentration of fine particles carried an increased lung cancer risk of 14%

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Air pollution - Addis Ababa

• Trend has been a constant decline in air quality since 1970

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• Population has been growing at a steady annual rate of more than 4% in the last decade

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• Currently the city has three functional reference-grade air quality monitoring stations for fine particulate matter (PM2.5), two established by the U.S. embassy in 2016, and a third monitoring station established by the Eastern Africa GEOHealth Hub in 2015.

O3 + PM + SO2 + NO2 + CO

• PM2.5 drives more than 70% of the health impacts associated with air pollution. The leading causes being – MI, Cancer, COPD, LRI, Stroke, Growth restriction, premature death

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• The PM2.5 pollution in Addis Ababa is constantly above the WHO’s annual mean guideline of 10 μg/m3 and is estimated to cause 10,000 to 20,000 premature deaths per year, in the city.

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• In 2005, the highest recommended average annual emission level for PM 2.5 was 10 μg/m3. The 2021 revision halves that number, to just 5 μg/m3.

The 24-hour level changed from 25 μg/m3 in 2005 to 15 μg/m3.

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Indoor pollution

Radon

• Radon a product of Uranium, accounts for around a half of all human exposure to radiation.

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• It is also the most important cause of lung cancer after smoking and the leading cause of lung cancer among non-smokers in the West.

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• According to WHO, radon is estimated to cause between 3% to 14% of all lung cancers

Asbestos

• Asbestos is a group of six naturally occurring fibrous minerals. It has been widely used in various industries due to its heat and corrosion-resistant properties.

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• It can be found in various building materials and vehicle products installed before 1981, such as thermal system insulation, roofing and siding shingles, vinyl floor tiles, plaster, cement, putties, and caulk

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• Asbestos becomes hazardous when it’s disturbed. The tiny fibers can be released into the air and inhaled or swallowed, leading to severe health complications, including lung cancer, mesothelioma, and asbestosis.

HIV

• Lung cancer is the third commonest HIV related cancer following NHL and Kaposi Sarcoma

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• Lung cancer now accounts for three times more cancer deaths than non‐Hodgkin's lymphoma

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• Accounts for 11–40% of deaths from non‐AIDS defining cancers, and 1.6–4.25% of all deaths in HIV+ patients

Risk Factors Continued

• Inflammations & benign Lung Ds- OR
• Chronic bronchitis (1.47), TB (1.48), pneumonia (1.57), Emphysema (2.44), a1 AT def (2), diffuse pulmonary fibrosis (8-14)

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• A first-degree relative of a lung cancer case confers a 2.4-fold higher lung cancer risk

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Screening

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• High risk individuals:
• Personal history of lung cancer (single biggest risk factor)
• Age > 55 years
• Total number of cigarettes smoked (cumulative)
• Concomitant COPD
• Family history of lung cancer
• Other significant or synergistic exposures (eg, asbestos)

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• ETS/TASH Eligibility criteria for lung cancer screening – Is being Validated

National Lung Screening Trial (NLST) and accumulated experience since that trial were published in 2011 have changed the approach to the early detection of primary lung malignancy��

• Lung (CT) Screening Reporting and Data System (Lung-RADS) has been widely adopted and standardized
• Nodule Size – 4mm >>> 6mm
• Nodule attenuation
• Nodule Morphology
• Nodule growth - the concept of doubling time.
• Malignant solid pulmonary nodules show doubling times between 20 and 400 days.
• Subsolid nodules, typically lesions along the adenocarcinoma spectrum, have longer doubling times, often more than 400 days and even as long as 1436 days.

Rounded atelectasis

Hamartoma

Volumetric multislice computed tomography

Bronchogenic carcinoma

Molecular Pathogenesis

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• “Driver mutations,” mutations in genes encoding signaling proteins that when aberrant, drive initiation and maintenance of tumor cells

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Mean age was 54 year, 61.6% were male, 25.3% had a prior history of smoking

A cross-sectional study conducted at TASH by Dr Tewodros and co.

Clinical manifestations

• Around 3/4^th of patients are symptomatic at presentation.

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• Intrathoracic effects
• The most common are cough(50-75%), hemoptysis(25-50%), dyspnea (25-50%) and chest pain (20%).

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• Predominance of local symptoms depend on the site &/or extent of invasion
• Central/endobronchial masses- Cough, hemoptysis, wheeze, stridor, dyspnea, or postobstructive pneumonitis.
• Peripheral masses - Pain from pleural or chest wall involvement, dyspnea on a restrictive basis, and symptoms of a lung abscess resulting from tumor cavitation

• Symptoms of local invasion

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• Hoarseness of voice (RLN), Superior vena cava syndrome (SCLC) and Pancoast syndrome(NSCLC).
• Pancoast tumor = Superior sulcus tumor. (Tumor arising above the pulmonary sulcus)
• Shoulder pain (most common), Horner’s syndrome and hand muscle atrophy.
• Horner’s syndrome- enophthalmos, ptosis, miosis, and anhydrosis.

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• Symptoms related to distant metastasis

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• Pleura, Bones, Adrenals, Liver and Brain

Symptoms of Paraneoplastic Syndromes

• Reported in 10–20% of bronchogenic tumor patients
• Musculoskeletal
• Clubbing, Hypertrophic pulmonary osteoarthropathy (HPO) – Large cell and Adenocarcinoma
• Hypercalcemia
• 2.5% of lung ca cases had tumor-induced hypercalcemia pred. Squamous cell histology
• SIADH
• Although only 10% of patients with SCLC exhibit SIADH secretion, SCLC accounts for approximately 75% of cases of SIADH

• Ectopic corticotropin secretion
• Of those with ectopic corticotropin secretion, SCLC accounts for 75% of cases, although only 1–2% of patients with SCLC develop Cushing syndrome. Cushing syndrome is seldom caused by NSCLC.

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• Neurologic Manifestations
• Variable and can affect any level of the central or peripheral nervous system.
• They include Lambert-Eaton myasthenic syndrome (LEMS), subacute sensory neuropathy, encephalomyelopathy, cerebellar degeneration, autonomic neuropathy, retinal degeneration, and opsoclonus.
• Their frequency in SCLC is approximately 5%
• Neurologic symptoms may precede the diagnosis by months to years.

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Evaluation of Lung Cancer Patients

• Non Invasive assessment
• CXR, CT scan, PET
• Semi- Invasive
• Bronchoscopy, Endobronchial Ultrasound, Trans Thoracic sampling
• Invasive
• Mediastinoscopy, Open surgery, Video assisted Thoracoscopy

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CXR - Right Upper Lobe Collapse

Non-invasive assessment - CT assessment�

TUMOR – Lung window

• Size
• Presence/absence of separate tumor nodule
• Presence/absence of atelectasis/obstructive pneumonia
• Possible invasion of adjacent structures
• Proximal extent of tumor

Node- Mediastinal window

Stations 1- 14

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Fluorodeoxyglucose positron emission tomography (PET)

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• For differentiating benign from malignant solid nodules 1 to 3 cm in size.

94% sensitive and 83% specific

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• False-positive PET results - granulomatous diseases such as tuberculosis, histoplasmosis, and sarcoidosis.
• False negative - minimally invasive adenocarcinoma, carcinoid tumors, and some metastases (e.g., renal cell carcinoma), small nodules (8-10mm)

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�Minimally invasive- Regular bronchoscopic biopsy�

For diagnosis of visible masses - endobronchial biopsy

Minimally invasive- Mediastinal staging by EBUS-TBNA

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EBUS for Station 7

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Herth FJ et al. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. J Bronchol 2006; 13(2): 84-91

Minimally invasive - Transthoracic lung biopsy

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Invasive - Surgical biopsy or resection

Approach to Staging

Quality Indicators

Therapeutic approach to lung cancer

• Tumor boards are the standard of care for cancer centers and large healthcare systems

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• Ensuring an individual can tolerate lung resection
• Traditional teaching states that a baseline forced expiratory volume in 1 second (FEV₁) > 1.5 L should be able to tolerate a lobectomy and an FEV₁ > 2.0 L should be able to tolerate a pneumonectomy

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• Management Depends on
• Cell type
• Tumor stage
• Molecular characteristics of the tumor
• Patients overall medical condition

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• Intention of management
• Early- curative- combinations of modalities
• Late- Palliative – Mostly chemo

Options for aggressive treatment

• Active cytotoxic agents
• Platinium compounds
• Cisplatin, carboplatin
• Taxans
• Docetaxel, paclitaxel, nanoparticle alb bound paclitaxel
• Gemcitabine
• Pemetrexel
• Camptothecins
• Irinotecan, topotecan

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• Targeted Agents
• EGFR- TKIs
• Erlotinib
• Gefitinib
• ALK fusion oncogene inhibition/ROS1
• Crizotinib

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• Monoclonal Abs
• Bevacizumab ( Binds VEGF)
• Cetuximab ( Binds EGFR)

Treatment of EGFR +ve NSCLC

Immunotherapy targets in NSCLC

PD-1 pathway

CTLA-4 pathway

APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte-associated antigen-4; �MHC, major histocompatibility complex; NSCLC, non-small cell lung cancer; �PD-1, programmed cell death protein-1; PD-L1, programmed cell death ligand-1;

1. Davies M. Cancer Manag Res 2014;6:63–75

Reprinted with permission from Dove Medical Press Ltd

CTLA-4 and PD-1 pathways are immune checkpoint pathways �that play critical roles in controlling T-cell immune responses¹

T-cells can become unresponsive after CTLA-4 binds B7 molecules on APC, �or when PD-1 binds PD-L1 or PDL-2 on target cells

Immunotherapy targets in NSCLC:

Anti-CTLA-4, PD-1, or PD-L1 antibodies can restore �T-cell activation and killing of tumor cells¹

APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte-associated antigen-4; �NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein-1;

PD-L1, programmed cell death ligand-1

1. Davies M. Cancer Manag Res 2014;6:63–75

• Anti-CTLA and -PD-1 antibodies are associated with unconventional response patterns and immune-related adverse events¹

Tumor cell

Tumor cell

Reprinted with permission from Dove Medical Press Ltd

Prevention

• Cigarette cessation programs
• Awareness creation (Mahfuz et al. unpublished)
• EVALUATING THE IMPACT OF GRAPHIC HEALTH WARNING LABELS INTENSITY ON ANTI-SMOKING INTENTIONS AMONG NON-SMOKING ADOLESCENTS ATTENDING HIGH SCHOOL IN ADDIS ABABA, ETHIOPIA: Quasi Experimental Study
• Stronger warnings were perceived as more effective tools of anti-smoking message communication.

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Thank You !!!!

Unlike direct PM measurements, AQI is a unitless number that varies from 0 to more than 500. PM2.5 AQI is a midnight-to-midnight 24-hour value based on 1-hour measured values. The PM2.5 AQI is computed from the following formula where Ip = AQI: