LUNG

CANCER
Supervised by: Dr. Azza

Presented by:
1. Muhammad Syamil (1129200919453)
2. Nurul Farhanim (1129200919568)
3. Sri Amelia (1129200919455)
4. Tuan Nur Syahirah (1129200919460)
5. M. Omar Hamwi (1129200919503)
6. Amir Farhan (1129200919452)
DEFINITION, EPIDEMIOLOGY
AND
RISK FACTORS
Prepared by
Muhammad Syamil,
1129200919453
 Lung cancer or bronchogenic carcinoma refers
to tumors originating in the lung parenchyma
or within the bronchi

Lung cancers usually are grouped into two

main types called small cell and non-small
Definition cell. These types of lung cancer grow
differently and are treated differently.
Non-small cell lung cancer is more common
than small cell lung cancer.
 EPIDEMIOLOGY OF LUNG CANCER
• A total of 11,256 cases of trachea, bronchus and lung cancers were registered for the period of 2012-
2016 compared with 10,608 cases in 2007-2011 report.
• 68.3% were among males and 31.7% were among females.
• It was the second most common cancer in males(The lifetime risk for males was 1 in 60) and fifth in
females(The lifetime risk for females was 1 in 138)
• According to the latest WHO data published in 2020 Lung Cancers Deaths in Malaysia reached 4,319 or
2.57% of total deaths. The age adjusted Death Rate is 15.25 per 100,000 of population which ranks
Malaysia 77 in the world
• the second most common cause of death due to cancer in the country after breast cancer, and the eighth
most common cause of death from all causes
• The 5-year observed survival rate is only 9.0% (95% confidence interval: 8.4– 9.7), whereas the 5-year
relative survival rate is 11.0% (95% confidence interval: 10.3–11.9)
• Historically, squamous cell carcinoma was the commonest lung cancer cell type. However, over the
years, adenocarcinoma has now replaced squamous cell carcinoma as the commonest lung cancer cell
type.
• An eight-year retrospective study done at University of Malaya Medical Center revealed
adenocarcinoma subtype as the most common cell type in all age groups
 REFERENCES
• Risk factors | Thoracic Tumours (esmo.org)
Pathophysiology
• The pathophysiology of lung cancer is very complex and
incompletely understood. It is hypothesized that repeated exposure
to carcinogens, such as cigarette smoke leads to dysplasia of lung
epithelium.
• If the exposure continues, it leads to genetic mutations and affects
protein synthesis.
• Then it disrupts the cell cycle and promotes carcinogenesis.
• The most common genetic mutations responsible for lung cancer
development are;
Small cell lung cancer (SCLC): MYC, BCL2, and p53
Non-small cell lung cancer (NSCLC): EGFR, KRAS, and p16
Sign and symptoms
Location Sign and symptoms

Endobronchial Cough, hemoptysis, bronchial obstruction, pneumonitis, pleural effusion

Mediastinal Dyspnea, postprandial cough, wheezing, stridor, hoarseness, and dysphagia

Bronchial and tracheal Bronchial and tracheal obstruction: change air flow and reduce oxygenation

Superior Vena Cava SVC syndrome: distended head and neck vein, blue discoloration of face and arm

Phrenic nerve Diaphragmatic paralysis

Sympathetic chain Horner syndrome; presented with ptosis, anhidrosis and miosis

Superior sulcus Shoulder pain and hand weakness seen branchial plexus involvement (Pancost tumor)
Physical examination
Extrapulmonary findings: adenopathy and clubbing.
Systemic findings: unexplained weight loss and low grade fever.
1. Head and neck
• If the cancer already spread to supraclavicular lymph node, it will give
enlargement to involve nodes.
Lymphatics
•Enlarged ipsilateral supraclavicular lymph nodes are included in limited-stage disease
•Enlarged axillary lymph nodes upstage the diagnosis to extensive stage disease
• Superior sulcus tumors, because of presence at the apex beat of the lung, can
compress the cervical sympathetic plexus causing Horner syndrome. ( ipsilateral
ptosis, miosis, enophthalmos, and anhidrosis.)
2. Cardiovascular examination
• Cardiac findings are usually noted when the tumor causes a
pericardial effusion. Findings can range from simple effusion to
tamponade. Direct cardiac involvement may also occur.
• Examination on extremities may reveal clubbing, cyanosis, or
edema. In the presence of superior vena cava (SVC) obstruction,
the right upper extremity is usually edematous.
• Heart sound is distant on auscultation
• JVP is raised, and paradoxically raised during inspiration
• Pulsus paradoxus classical sign of pericardial tamponade
3. Respiratory system
• Centrally located obstructing tumors can cause collapsed of entire lung
with an absent of breath sound on the side of lesion. Peripheral lesion
can cause individual segment or lobes to collapse, leading to findings
of dullness on percussion and reduce breath sound on auscultation.
• Pleural effusion give rise to characteristic findings of stony dullness and
reduce breath sound, depending on the size.
• Respiratory insufficiency is signaled by dyspnea and increased work of
breathing, retractions, orthopnea, and cyanosis.
Upper airway obstruction: stridor and wheezing.
Lower airway obstruction: asymmetric breath sounds
• Patient usually experience shortness of breath causing used of
accessory muscle for respiration and flaring of the nasal alae
• Distal atelectasis, post obstructive pneumonia and pleural effusion
the examination reveals stony dullness on percussion and reduce
breath sound.
4. Gastrointestinal system
• Liver is a common site of metastatic spread. On physical
examination may reveal yellowish discoloration and
hepatomegaly .
• Most often no specific findings on GI tract on examination.
• Very often patients are asymptomatic but may have elevated
liver enzyme levels.
5. Central Nervous System
• Physical findings depend on the site of the brain lesion.
• Perform fundoscopy to look for sign of raise intracranial pressure,
as well as neurological examination and evaluation of cerebellar
function, coordination and gait.
6. Musculoskeletal System
• Bone is another common site of spread for lung carcinomas.
• Patients may report bone pain, and tender spots may be found
during examination. The examination should include fist
percussion of the spine to look for tender spots, which may
suggest vertebral column metastases.
Investigation: Laboratory Tests How about
tumor marker?
• Complete Blood Count:
to check red/white blood cell & platelets
to check bone marrow and organ function
• Blood Chemistry Test (LFT, U&E): to assess how organs are
functioning such as liver and kidney
• Biopsy histopathological exam
-to determine if the tumor is cancer or not
-to determine the type of cancer
-to determine the grade of cancer (slow or fast)
 Investigation: Imaging Tests
• Chest X-Ray: This is often the first test will do to look for any
abnormal areas in the lungs.
• CT scan: Can show the size, shape, and position of any lung
tumors and can help find enlarged lymph nodes.
• MRI scan: used to look for possible spread of lung cancer to
the brain or spinal cord.
• PET scan:- A form of radioactive sugar (known as FDG) is
injected into the blood - Cancer cells needs a lot of energy so
they take up this special sugar.
https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/diagnosing-lung-cancer/imaging-tests
 Investigation: Specialised Tests
• Bronchoscopy: Any abnormal findings may be
biopsied and sent to the lab to determine if any
cancer cells are present in the airways.

• Needle biopsy: can often use a hollow needle

to get a small sample from a suspicious area
(mass).
1. Fine needle aspiration (FNA) - collect cells sample
2. Core needle biopsy – collect core of tissue
3. Open (surgical biopsy) - remove part/all mass.
 Small cell lung Ca Non-small cell lung Ca
(SCLC) (NSCLC)
Scanty cytoplasm, Abundant cytoplasm
Histo- fixed shaped nuclei Pleomorphic nuclei
pathological Fine Chromatin Coarse Chromatin
Examination Nucleoli indistinct Nucleoli is prominent
Architecture: Diffuse Architecture: glandular or
sheets of cells squamous
Chemotherapy Responds better Responds less
& Radiation:
Neuroendocrine Usually present Usually absent
markers
Epithelial markers Usually absent Usually present
Distinctive microscopic findings
• Squamous cell carcinoma is characterized by presence of
keratin pearl formation and/or intercellular bridge
• Adenocarcinoma is characterized by formation of glandular
structures by tumor cells with or without mucin secretion
• Large cell carcinoma is characterized by tumor cells with
abundant cytoplasm and lack of granular or
squamous differentiation
• Small cell carcinoma is characterized by clusters/sheets of
small cells with increased NC ratio.
STAGING NSCLC
TAGING NSCLC & PROGNOSI
 STAGING SCLC
• Limited
 Cancer is in one lung, the mediastinum, and local lymph nodes.
 Treatment: chemotherapy plus radiotherapy, and such therapy can cure
20–25% of patients
• Extensive
 Cancer has spread beyond one lung, the mediastinum and local lymph
nodes.
 Common spread to the liver, bones, adrenal glands, and brain
 Treatment: Extensive-stage SCLC is incurable, but chemotherapy can
improve quality of life and prolong life.
Kalemkerian GP. Staging and imaging of small cell lung cancer. Cancer Imaging. 2012 Jan 12;11(1):253-8. doi: 10.1102/1470-
7330.2011.0036. PMID: 22245990; PMCID: PMC3266593.
 Differential Diagnosis of Lung Cancer
Differential Positive Negative Radiology Characteristic feature
diagnosis symptoms symptoms findings
- Low grade fever - Coin-shaped - Long h/o smoking
- Dry/productive lesion - Elderly male or female
Primary lung cough - Thick - CT guided biopsy is
cancer - Hemoptysis wall(>15mm) required.
(malignancy) - Weight loss - Ground glass
- Night sweat opacities

- Productive - High grade - irregularly - Foul smelling sputum

cough fever shaped thick - H/o of
- Night sweat -Hemoptysis walled cavity prior infection or hospitali
Acute lung - Weight loss - Chest pain with an air-fluid zation
abscess level - Associated with risk
factors like aspiration and
alcoholism
 Differential Diagnosis of Lung Cancer
Differential Positive Negative Radiology Characteristic feature
diagnosis symptoms symptoms findings
-Productive - High - Cavitations in - People in endemic at
cough ​ grade fever​ the upper high risk​
- Hemoptysis​ ​ lobe of the lung​ - Cough >2
Pulmonary - Weight loss​ weeks hemoptysis​
Tuberculosis​ - Night sweat​ - Positive AFB

-Dry/productive - Fever ​ - Tram tracking - CT confirms the

cough​ - Weight appearance​ diagnosis​
- Hemoptysis​ loss​ -Increased ​
Bronchiectasis​ - Night pulmonary
sweat​ markings​
- Honeycombing​
Complications of Lung Cancer
Symptoms:
Localised
Shortness of Breath
Ø Recurrent laryngeal nerve palsy Hemoptysis
Ø SVC obstruction Chest pain
Pleural effusion
Ø Horner syndrome Hypercalcemia
Ø Pericarditis

Metastatic
Ø Brain, Bone, Liver, Adrenal gland
Mesothelioma Diagnosis
• Chest X-ray & contract enhanced CT scan: Pleural thickening
or recurrent pleural effusion.

• Thoracocentesis acquiring pleural fluid for cytology.

• Pleural biopsy (e.g., video assisted thoracoscopic surgery

[preferred], CT guided core biopsy, open biopsy.
 Mesothelioma Radiology:

(a) patient with a small pleural effusion with

(a) Chest radiograph shows a small loculated visceral and parietal pleural thickening
right pleural effusion. (b) Chest radiograph (arrowhead) that involves the anterior
shows extensive circumferential right mediastinal pleura (arrow). (b) Focal pleural
pleural thickening with associated volume thickening (arrow) with evidence of invasion
loss of the right hemithorax. through the chest wall.
 References
• Sakashita, S., Sakashita, M., & Sound Tsao, M.
(2014). Genes and Pathology of Non-Small Cell Lung
Carcinoma. Seminars in Oncology, 41(1), 28–39.
doi:10.1053/j.seminoncol.2013.12.008
• Kalemkerian, G. P. (2011). Staging and imaging of
small cell lung cancer. Cancer Imaging, 11(1), 253–
258. https://doi.org/10.1102/1470-7330.2011.0036
• I‌maging Tests | LUNGevity Foundation. (2021).
Retrieved October 29, 2022, from
Lungevity.org website:
https://www.lungevity.org/for-patients-caregivers/l
ung-cancer-101/diagnosing-lung-cancer/imaging-tes
ts
• Sinha, S., Swift, A. J., Kamil, M. A., Matthews, S.,
Bull, M. J., Fisher, P., … Johns, C. S. (2020). The role
of imaging in malignant pleural mesothelioma: an
update after the 2018 BTS guidelines. Clinical
Radiology, 75(6),
423–432. doi:10.1016/j.crad.2019.12.001
Management & Treatment of NSCLC
Stages of NSCLC Treatment Recommendations
Stage 0 – Stage IA Surgery without Adjuvant chemotherapy

*benefit of adding adjuvant chemotherapy increases

as disease stage increase
Stage IB (>4cm tumor size) or Stage II 1. Surgery

2. Adjuvant & Neoadjuvant chemotherapy regimens:

Adjuvant (4 cycles)
• Cisplastin 50mg/m2 IV on days 1 & 8 PLUS
Vinorelbine 25mg/m2 on days 1,8,15,22 every 28 d
or
• Cisplastin 100mg/m2 IV on day 1 PLUS etoposide
100mg/m2 IV on days 1 and 8 every 21 d
Neoadjuvant chemotherapy (3 cycles)
• Nivolumab 360mg IV q3weeks PLUS Platinum-
doublet chemotherapy q3weeks
Platinum-doublet chemotherapy:
• Any Histology:
 Paclitaxel 175-200mg/m2 and Carboplatin area
under the curve (AUC) 5 or 6
• Non-squamous histology:
 Pametrexed 500mg/m2 and cisplastin 75mg/m2
• Squamous histology:
 Gemcitabine 1000-1250 mg/m2 and cisplastin
75mg/m2
 Stages of NSCLC Treatment Recommendations
Stage IIIA or IIIB Treated with combination of chemotherapy and
radiation therapy

Concurrent chemotherapy/radiation therapy

regimens:
• Cisplatin 50 mg/m2 IV on days 1, 8, 29, and 36 plus
etoposide 50 mg/m2 IV on days 1-5 and days 29-33
• Carboplatin AUC 2 IV weekly for 7 week plus
paclitaxel 45 - 50 mg/m2 IV weekly for 7 weeks; 3
weeks later, it can be followed by two cycles of
consolidation chemotherapy with carboplatin AUC
6 IV on day 1 plus paclitaxel 200 mg/m2 IV on day 1
every 21 week
Sequential chemotherapy/radiation therapy
regimens:
• Cisplatin 100 mg/m2 IV on days 1 and 29 plus
vinblastine 5 mg/m2/weekly IV on days 1, 8, 15,
22, and 29, followed by radiation therapy

Consolidation therapy:
Durvalumab is given as follows for up to 12 months:
• Patients weighing ≥30 kg: 10 mg/kg IV q2wk or
1500 mg IV q4wk infused over 60 min
• Patients weighing < 30 kg: 10 mg/kg IV q2wk
infused over 60 min
 Stages of NSCLC Treatment Recommendations
Stage IV and Recurrent Disease First-line treatment options if not a candidate
for targeted therapy:
Patients with advanced or recurrent disease • Cisplatin 75 mg/m2 IV on day 1 PLUS
with actionable oncogenes: treat with paclitaxel 175 mg/m2 IV on day 1 every 21 d
targeted therapy.
Combination immunotherapy for first-line
Patients without an actionable genetic treatment of metastatic NSCLC with PD-L1
alteration: treated with chemotherapy tumor expression ≥1% :
alone, chemotherapy with immunotherapy, • Nivolumab 3 mg/kg IV q2wk,
or immunotherapy alone. plus Ipilimumab 1 mg/kg IV q6wk

Patients with poor performance status or First-line treatment of metastatic squamous

co-morbidities: considered for single-agent NSCLC:
chemotherapy, immunotherapy, or (if they • Paclitaxel protein bound 100 mg/m2 IV on
have an actionable oncogene) targeted days 1, 8, and 15 of every 21 d plus
therapy. carboplatin AUC 6 IV on day 1
Patients with nonsquamous NSCLC without EGFR or
ALK genomic tumor aberrations:
• Pembrolizumab 200 mg plus pemetrexed 500
mg/m2 plus cisplatin 75 mg/m2 IV on day 1 every 21
d for four cycles (plus folate and vitamin B12
supplements along with dexamethasone
premedication for pemetrexed)

Patients with nonsquamous NSCLC with EGFR or ALK

genomic tumor aberrations:
• Pemetrexed 500 mg/m 2 IV administered 10 minutes
before cisplatin 75 mg/m2 IV on day 1 every 21 d for
up to six cycles in the absence of disease progression
or unacceptable toxicity

Single-agent regimens:
• Paclitaxel 200 mg/m2 IV every 21 d or
• Docetaxel 35 mg/m2 IV weekly for 3 wk every 4wk
 Management & Treatment of SCLC
Stages Treatment

Limited-Stage SCLC Stages I-III:

o Treated with systemic therapy, with or without
radiation therapy
o Chemotherapy and radiation therapy are typically
given concurrently, but some patients unable to
tolerate chemoradiation (chemotherapy
then radiation therapy)
o Clinical stage I - IIA patients-undergo pathological
mediastinal staging to determine whether there is
mediastinal lymph node involvement.
o Negative-lobectomy with mediastinal lymph
node dissection or sampling
Stages Treatment

Limited-Stage SCLC Concurrent chemotherapy recommendations with

radiation:
• Cisplatin 60 mg/m2 IV on day 1 plus etoposide 120
mg/m2 IV on days 1-3 every 21-28d
• Carboplatin area under the curve (AUC) 5-6 IV day
1 plus etoposide 100 mg/m2 IV days 1-3 every 21-
28d
• Chemotherapy should be given up to four to six
cycles.
• Radiotherapy for limited-stage disease should start
with cycle 1 or 2 of chemotherapy.
Stages Treatment

Limited-Stage SCLC Chemotherapy recommendations for patients not able

to tolerate concurrent chemotherapy and radiation:
• Patients with limited-stage (stages I–III) disease who
are not able to tolerate chemotherapy and radiation
concurrently should be treated with chemotherapy
as first-line therapy
• Cisplatin 60-80 mg/m2 IV on day 1 plus etoposide 80-
120 mg/m2 IV on days 1-3 every 21-28d
• Carboplatin AUC 5-6 IV on day 1 plus etoposide 80-
100 mg/m2 IV on days 1-3 every 28d
Stages Treatment

Extensive- Stage IV
stage Should be given for a maximum of four to six cycles:
SCLC • Atezolizumab1200 mg IV on day 1 plus carboplatin AUC 5 on day
1 plus etoposide 100 mg/m2 IV on days 1-3 every 21d x four cycles; follow
with maintenance atezolizumab every 21d
• Durvalumab1500 mg IV
• Cisplatin 60-80 mg/m2 IV on day 1 plus etoposide 80-120 mg/m2 IV on
days 1-3 every 21-28d
• Carboplatin AUC 5-6 IV on day 1 plus etoposide 80-100 mg/m2 IV on days
1-3 every 28d
• Cisplatin 60 mg/m2 IV on day 1 plus irinotecan 60 mg/m2 IV on days 1, 8,
and 15 every 28d
• Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day
1 plus irinotecan 65 mg/m2 IV on days 1 and 8 every 21d
Stages Treatment

Extensive- o Second-line chemotherapy is given for at least 4-6 cycles but can be given
stage until disease progression as tolerated in some cases
SCLC o Patients who have relapsed disease more than 6mo after completing first-
line chemotherapy can be treated with that original first-line regimen
(typically a platinum-based doublet) again, with an expected response
rate of 62-100%
Common side effects of treatment
Follow Up
Follow-Up After Therapy for Patients with Non-Small Cell Lung Cancer (NSCLC)

Studies have shown 6.5% annual recurrence rate of NSCLC stage I and SCLC, respectively

• Observation for complications of treatment is recommended for at least 3-6 months

• Follow up with history, physical exam and chest computed tomography (CT) scan with
or without contrast is advised every 6 months for 2-3 years
• Then history, physical exam and low-dose chest CT scan without contrast annually
thereafter for patients with stage I-II NSCLC given primary treatment including surgery
with or without chemotherapy
 High-resolution CT scan is recommended 4 years after surgical resection of stages
IA to IIIA NSCLC, followed by low dose computed tomography (LDCT) every year
starting in the 5th year
 Peak incidence of recurrence is between 2 and 3 years
• Patients with stage I-II NSCLC --> given primary treatment with radiotherapy

• Patients diagnosed with stage III or IV NSCLC --> history, PE, and chest CT scan with or
without contrast is advised every 3-6 months for 3 years
 Then history, PE and chest CT scan with or without contrast every 6 months for 2
years, then history and PE with low-dose chest CT scan without contrast annually

• Patients with advanced or metastatic disease, response to initial therapy should be

assessed after 2 cycles using CT with or without contrast on previously identified tumor
sites, then every 2-4 cycles or when clinically indicated
 Assessment of response to subsequent therapy should be done every 6-12 weeks
using CT with or without contrast on previously identified tumor sites

• It is recommended that all screening and follow-up CT scans should be performed at

a dose of 100-120 kVp and 40-60 mAs or less
• Biomarkers
 ALK fusion oncogene
 ROS1 gene rearrangements
 BRAF V600E mutations
 EGFR mutations
 PD-1 ligand
*utilized to predict treatment outcome or disease prognosis​

• Patients who smoke should be advised to quit​

Follow-Up After Therapy for Patients with Small Cell Lung Cancer (SCLC)

• Patients with limited disease (LD) --> follow up every 3 months for the 1st year or two,
then every 6 months during the 3rd year, then annually after recovery

• Patients with extensive disease (ED) --> follow up every 2 months during the 1st year,
then every 3-4 months on years 2-3, then every 6 months on years 4-5, then annually

• It is recommended that all screening and follow-up CT scans should be performed at a

dose of 100-120 kVp and 40-60 mAs or less
• Response assessment using chest, pelvic and abdominal CT scan with contrast, or
brain MRI or CT with contrast depends on previous treatment given and stage of
patient's disease:
 LD SCLC patients given adjuvant chemotherapy or chemoradiotherapy: Only
after completion of treatments
 LD SCLC patients given systemic therapy or chemoradiotherapy: After every 2
cycles of systemic therapy and at completion of treatments
 ED SCLC patients given systemic therapy: After every 2-3 cycles of systemic
therapy and at completion of therapy

• Response assessment of ED SCLC patients with asymptomatic brain metastasis

receiving systemic therapy prior to WBRT should undergo brain magnetic
resonance imaging (MRI) or CT scan with contrast every 2 cycles of chemotherapy
and after completion of therapy
Palliative Care for Lung Cancer
• Procedures to open airways
• Medications to treat pain
• Medications to suppress a cough, open closed airways and improve
breathing
• Emotional support and counselling
• Nutritional supplements to reduce weight loss
• Medications to reduce nausea
• Integrative services like massage, mindfulness
References
• Lung Cancer Management, Follow Up And Prevention | MIMS Malaysia
(2022). From https://specialty.mims.com/lung%20cancer/management
• Supportive (Palliative) Care for Lung Cancer American Lung Association (2022).
From
https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/treat
ment/types-of-treatment/supportive-palliative-care

• Prevention, diagnosis, therapy, and follow-up of lung cancer: interdisciplinary

guideline of the German Respiratory Society and the German Cancer Society.:
Semantic Scholar (2011). From
https://www.semanticscholar.org/paper/Prevention%2C-diagnosis%2C-therapy%2C
-and-follow-up-of-of-Goeckenjan-Sitter/70f0fbb158db783d58d32365c727da5bba3d
a55d

• https://emedicine.medscape.com/article/279960-clinical#b3