lung cancer pathology & treatment

1. Lung
Cancer

2. Epidemiology
LungCancer is a leading cause of
death
Mortality Rate of 40%
Survival Rate Of 18 %
Lung cancer (both small cell and non-small cell) is the second most common cancerin both menand women(not
counting skin cancer). Inmen, prostate cancer is more common, while in women breast cancer is more common.
The American CancerSociety’sestimatesfor lungcancer in the UnitedStatesfor 2022 are:
• About 236,740 new cases of lung cancer(117,910 in men and118,830 in women)
• About 130,180 deathsfrom lung cancer (68,820 in men and61,360 in women)
Lung cancer is by far the leadingcause of cancer deathamongboth men and women, making up almost 25%of all cancer
deaths. Each year, more people die of lung cancer thanof colon, breast, and prostate cancerscombined.

3. Types of Lung Cancer
There are 2 main types of lung cancer andthey are treatedvery differently.
Non-smallcelllung cancer(NSCLC)
About 80% to85% of lung cancers are NSCLC. The main subtypesof NSCLC are adenocarcinoma, squamouscell carcinoma, and
large cell carcinoma. These subtypes, which start from different types of lung cellsare grouped together asNSCLC because
their treatment andprognoses are often similar.
Adenocarcinoma:Adenocarcinomas start in the cellsthat wouldnormally secrete
Substancessuch as mucus. This type of lung cancer occurs mainly in people who currently smoke or formerly Smoked. It is
more common in women than in men, andit is more likely tooccur in Younger people than other types of lung cancer.
Squamouscellcarcinoma: Squamouscell carcinomas start in squamous cells, which are flat cells that line the inside of the
airwaysin the lungs. They are often linkedto a History of smoking and tendto be found in the central part of the lungs, near a
main airway (bronchus).
Largecell (undifferentiated) carcinoma:Large cell carcinoma can appearin any part of the lung. It tendsto grow and
spread quickly, which can make it harder totreat. A subtype of large cell carcinoma, known aslarge cellneuroendocrine
carcinoma, isa fast-growing cancer that is very similar tosmall cell lung cancer.

4. Smallcelllung cancer(SCLC)
About 10% to15% of all lungcancers are SCLC andit is sometimes calledoatcell cancer.Thistype of lung cancer tendsto grow
and spreadfaster than NSCLC. About 70%of people with SCLC will have cancer that hasalready spreadat the time they are
diagnosed. Since this cancergrows quickly, it tends to respond well tochemotherapy andradiationtherapy .Unfortunately, for
most people, the cancer will return at some point

5. Pathophysiology
The pathophysiology of lung cancer refers to
➢ the physical changes happening in the body
that lead to lung cancer.
• The leading cause of lung cancer is
exposure to tobacco smoke. Other possible
causes include radon, asbestos, radiation,
and air pollution.
• Gene mutations, either inherited or
acquired, may raise your risk of developing
lung cancer.

6. Risk Factors
Smoking
Exposure to tobacco smoke is the
leading risk factor for developing
lungcancer.
83 %
Asbestos
Asbestosis a groupof naturally
occurring mineralsthat arelikelyfound
in placeswherepeoplework with
insulation.
6 %
SecondHand Smoking
Secondhandsmoke canraiseyour riskof
developing lung cancer.leadsto7,000
deathsfrom lung cancereachyear.
3 %
others
8 %

7. Inherited Gene Mutation
It’spossible to inherit a DNA mutationfrom one or both of your parents. It’simportant to note that inheritedmutations alone
usually do not leadto cancer. They simply increase our risk. People whoinherit a mutationin chromosome 6 are more likely to
developlungcancer evenif they do not smoke tobacco.
Otherinheritedmutations include people whose bodies cannot breakdownsome of the chemicals found in cigarettesor who
cannot repair damagedDNA.
Some forms of non-small cell lung cancer cause the epidermal growthfactor receptor(EGFR) gene to produce too much EGFR
protein in the body. This is often seenin individuals with adenocarcinoma whodo not have a history of smoking.

8. AcquiredGene Mutation
While it is possible to inherit a gene mutation that canleadto cancer, most gene mutations are acquired overa lifetime. These
mutations oftenoccur due to environmental exposuresandcause changes in the DNA of lung cells. These changes can then
leadtoabnormal cell growthand possibly cancer.
DNAis a chemical in our cellsthat makesup our genes. We inherit DNAfrom both of our parents, and it caninfluence our risk of
developingseveral chronic diseases, including cancer. The genesinvolved in cancer are:
• Oncogenes, whichhelpcellsto grow and divide.
• Tumorsuppressorgenes, which helpcontrol cell division andcause cellsto die at the right time.
Gene mutationsthat may leadtolung cancerinclude:
• RB1 tumor suppressorgene: Small cell lungcancer
• p16 tumor suppressorgene: Non-small cell lungcancer
• K-RAS oncogene: Non-small cell lungcancer
• TP53 tumor suppression gene: Bothsmall cell lungcancerand non-small cell lung cancer
Besidesmutations, gene alterations—like translocations, forexample—may alsoincrease the risk of lung cancer. Examplesof
common translocationsinclude:
• ALKgene: Non-small cell lungcancer
• Chromosome 3: Bothsmall cell lungcancer andnon-small cell lungcancer

9. Screening
2013 guidelines by the American
College of Chest Physicians
● How? – Low dose ComputedTomography (LDCT)
● How Often? – Annually
● For Whom? – Pts whoare 55 to 74 yearsold
who:
● Have Smokedfor 30pack years andstill smoke or
● Have stoppedsmoking during the last 15 years.

10. Diagnosis
PETScan
CT Scan
Physical Examination
Lung Biopsy
Lung X-ray
A chest x-ray isoften thefirst test your
doctorwill do to look for any abnormal
areasinthe lungs.Ifsomething suspicious
isseen, your doctormay ordermoretests.
CTscanner takes many pictures and a computer
then combines them to show a slice of the part of
your body being studied.
A CTscan is more likely to show lungtumors than
routine chest x-rays.It can also show thesize,
shape, and position of any lungtumors and can
help find enlarged lymph nodes that might
contain cancer that has spread.This test can also
be usedto look for masses in the adrenal glands,
liver, brain, andother organs that might be due to
the lung cancer spread
Your doctorwill alsoexamineyouto look for signs
of lung canceror otherhealthproblems.Ifthe
resultsof your historyand physical exam suggest
you might havelung cancer,moretestswill be
done.
Doctors often use a hollow needle to get a small
sample from a suspicious area (mass).
An advantage of needle biopsies is that they don’t
require a surgical incision. The drawback is that they
remove only a small amount of tissue and in some
cases, the amount of tissue removed might not be
enough to both make a diagnosis and to perform
more tests on the cancer cells that can help doctors
choose anticancer drugs
Using 18F-fluorodeoxyglucose, Cancer cells eat
a lot of glucose and shine onthe PETScan

11. Complications
• Paraneoplastic Syndrome.
• Metastases.
Primary lung cancer metastasize to:
✓ Hilar lymph nodes (painless lymphadenopathy)
✓ Adrenals
✓ Liver
✓ Brain
✓ Bone (Osteolytic lesions)
• Cachexia
• Anemia
• Complications Of treatment
• Death

12. Staging
StageI
Tumor less than 3 cm,
There is no metastasis
StageII
Tumor less than 6 cm,
single metastases are
observed
StageIII
Tumor more than 6 cm,
metastases in lymph
nodes
StageIV
The tumor passed to
other organs

13. 1 2
3
4
5
6
7
Symptoms
Fatigue
Back, Shoulder, Chest Pain
Presistant Cough
ShortnessOf Breath
Repeated Respiratory Infections
Coughthat does not go away
or get worse
Hoarseness

14. Management Of small Cell Lung Cancer
TNM – Stage I - III
Early-stage disease witha more centrally
located tumor and locally advanced
disease are managed witha combinationof
chemotherapy and radiotherapy
(chemoradiotherapy), withthe optionof
prophylacticcranial irradiationto reduce
the risk of brain metastases
Recurrent Disease
Recurrent disease is treated with
chemotherapy (second line: topotecan or
lurbinectedin)nivolumabor
immunotherapy(third line:
pembrolizumab)
TNM – Stage I
Early-stage disease witha more peripherally
located tumor is amenable to surgery and
stereotactic ablativeradiotherapy, with
adjuvantchemotherapy.
TNM – Stage IV
Metastatic disease is treated witha
combinationof chemotherapy and immune
checkpoint inhibitors(such as PDL1
inhibitors),withadjuvantimmunotherapy and
possibly radiotherapy

15. Management Of NON-SmallCell Lung Cancer
TNM – Stage II
• Surgery.
• Chemotherapy followed by surgery.
• Surgery Followed By chemotherapy.
• Surgery Followed by EGFR tyrosine kinase
inhibitor.
TNM – IV &Recurrent
Disease
• Combination chemotherapy and targeted therapy with
a monoclonal antibody, such as bevacizumab.
• Combination chemotherapy followed by
more chemotherapy as maintenance therapy to help
keep cancer from progressing.
• Targeted therapy with an EGFR tyrosine kinase
inhibitor, such as osimertinib.
• Targeted therapy with an ALK inhibitor, such
as alectinib.
• Targeted therapy with a BRAF inhibitor or MEK
inhibitor, such as dabrafenib.
TNM – Stage I
Surgery Followed By targeted therapy with an EGFR
Tyrosine Kinase inhibitor such as Osimertinib.
TNM – Stage III
Can be removed with surgery may include the following:
Chemotherapy followed by surgery.
• Chemotherapy and radiation therapy followed by
surgery.
• Surgery followed by chemotherapy.
• Surgery followed by targeted therapy with an EGFR
tyrosine kinase inhibitor, such as osimertinib.
• Surgery followed by chemotherapy combined with
radiation therapy.
• Chemotherapy and radiation therapy followed
by immunotherapy with an immune checkpoint
inhibitor, such as durvalumab.

16. Post Treatment
Follow-up
● 1st 2 years : physical exam + CXR 4 times/yr.
● 3rd, 4th, 5th year: CXR twice/yr.
● >5th year: CXR once/yr.
[You can substitute CT for 1CXR per year]

17. Prevention
StopAlcohol
StopSmoking
Eat Vegitables,
Whole Grains
and legumes
Avoid Second
Hand Smoking
Exercise
Regularly
Weight Control

18. Question 1
Which of the following is the most
common cause of occupational
lung cancer :
a) Asbestosis
b) Silicosis
c) Radon Gas
d) Beryllium
Answer : Asbestosis

19. Question 2
Which of the following is the
standard of care foe health
patient with a clinical stage I
NSLC:
a) Surgical resection
b) SBRT
c) Chemotherapy
d) Immunotherapy
Answer : Surgical resection

20. Question 3
Surgery is the treatment of choicefor stage
II NSCLC. As an adjuvant therapy which
of the following is the recommended in
completelyresected stag II NSCLC:
a) Chemo radiation
b) Radiotherapy
c) Chemotherapy
d) Non of the above
Answer : Chemotherapy

21. Question 4
In term of the number of cancer related
deaths worldwide, where dose lung
cancer rank :
a) First
b) Second after colorectal cancer
c) Third after colorectal cancer
and stomach cancer
Answer : First

22. Question 5
Whichof the following are possible
treatments options for lung cancer:
a) Targeted treatments
b) Immunotherapy
c) Radiation
d) All Of the above
Answer : All of the above

23. Question 6
In Whichof the following mutation or
translocationcan lead to SCLC :
a) Chromosome 3
b) TP53
c) K-RAS
d) RB1
e) All Of the above
Answer : RB1

24. Question 7
What is recommended Diagnosis for lung
cancer :
a) X-Ray
b) CT
c) LFTs
d) All of the above
Answer: CT

25. Question 8
What is recommended screening test for
lung cancer :
Answer :
Low dose Computed Tomography

26. Prepared By
MahmoudAbdelgied, Mohamed Abdalkarim, Ahmed Haraza,
Mohamed Megahed, SherifThabet,Abdelrahman Samir,
Marwan Shaaban,ElwaliedTalal, Mostafa Gaber.
Students, FayoumUniversity, FacultyOf Pharmacy, 5th
Grad,
Clinical, 2021/2022
Under Supervision Of Clinical Pharmacy Department

27. THANK YOU
For more informationsabout
lung cancer,
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