The document discusses lung tumors and lung cancer. It describes that lung neoplasms can be benign or malignant. Benign lung tumors are commonly asymptomatic and incidentally found on imaging. They are divided into epithelial and non-epithelial tumors, with hamartomas making up about 50% of benign lung neoplasms. The document then discusses the classification, characteristics, and treatment of various benign lung tumors such as papillomas, micronodular pneumocyte hyperplasia, and hamartomas. It also provides details on the epidemiology, risk factors, histological types including adenocarcinoma and small cell lung cancer, etiology related to smoking, and clinical presentation of lung cancer.

1. lung tumors
Prepared by
Dr Hemin Khalid Saber

3.  Lung neoplasms can be classified as benign or
malignant.
 Most benign lung tumors present as
asymptomatic solitary pulmonary nodules,
 incidentally discovered radiographically. About
50% of benign lung neoplasms are
hamartomas.

6.  Benign lung tumors are broadly divided into
epithelial and nonepithelial tumors.
EPITHELIAL NEOPLASMS
Types include:
Papilloma
Micronodular pneumocyte hyperplasia
NONEPITHELIAL NEOPLASMS
Types include:
Hamartomas
Solitary fibrous tumors

7. Papillomas
 SQUAMOUS PAPILLOMA—Most often
associated with cigarette smoking and human
papilloma virus. Most occur in central large
airways.

8. RECURRENT RESPIRATORY
PAPILLOMATOSIS.
 Associated with human papilloma virus types 11
and 6.
 Surgical excision and laser ablation are the
mainstays of treatment.
 Squamous cell carcinoma is the most feared
complication and may appear as cavitating nodules
or masses

10. Micronodular Pneumocyte
Hyperplasia
 Characterized by numerous small, well-
demarcated parenchymal nodules.
 Classically associated with tuberous sclerosis
and/or lymphangioleiomyomatosis.
 Histopathology shows hyperplastic type II
pneumocytes.
 Findings are not progressive, so no treatment
is indicated.

11. Hamartoma

15. Bronchogenic carcinoma

16. Epidemiology of
Lung Cancer
 Lung cancer is the leading cause of cancer
death worldwide
 Cancer of the lung and bronchus ranked second
in cancer incidence in both sexes, with an
estimated cases in males (14% of all new
cancers) and in females (13-14% of all new
cancers)

17. Estimated new cancer cases

18. Epidemiology of
Lung Cancer
 Lung cancer ranked as number one in causing
deaths in both sexes yearly 27-28% and
26%of all cancer deaths for males and females)

19. Estimated death rate

20. Epidemiology of
Lung Cancer

21. Classification of ca bron.

22. Central
Squ.ca
Sm.ca
Peripheral
Aden,larg.

23. Histological class.

24.  In the recent past, a relative increase in the incidence
of ADC has been witnessed
 In most of the developed countries, it has become the
dominant histological type of lung cancer
 overtaken SqCC . among males in some countries
while it has continued to be the commonest type
among females

25.  Link between Histology and Smoking
 Use – filters--- lower content of tar and nicotine
resulted in a tendency for their smoke to be
inhaled more deeply
 hig.concen. of carcinogens in the perip.

26. Adenocarcinoma
 Adenocarcinoma is the most frequently
diagnosed histologic type of lung cancer.
 It is the most common subtype in women and
nonsmokers.
 Most tumors occur in the periphery.
 Positive immunohistochemical stains include
thyroid transcription factor-1, napsin A, and
cytokeratin 7.

48. Squamous Cell Carcinoma
(SCC)
 Central mass, but approximately 25% are
located peripherally and 5% show central
cavitation.
 Histologically, two features are important for
diagnosis;
 keratinization and intercellular bridges.

49. Histopathologic specimen of squamous cell carcinoma of the lung
with intercellular bridges (arrow).

51. Squamous Cell Carcinoma
(SCC)
 The WHO classification recognizes four
variants namely; papillary, clear cell, small
cell and basaloid.
 The small cell variant of Scc poorly
differentiated variant which contains small
tumor cells but retains cellular characteristics
of a non-SCC such as coarse chromatin,
nucleoli and distinct cell borders

52.  Compared with hist. subtypes, commonly
assoc, cavitation, Pancoast syndrome, and
hypercalcemia.
 Immunohistochemistry: Usually stains
positive for p63, cytokeratin 5/6.
<

53. Large Cell Carcinoma
 Undifferentiated malignant epithelial tumors
that lack features of small cell carcinoma and
glandular or squamous differentiation.
 They are characterized by large nuclei,
prominent nucleoli, and a moderate amount
of cytoplasm.

54.  These tumors are usually peripherally located
with pleural and chest wall invasion.
 The tumor cells do not show intercellular
bridges or keratinizations which are
characteristic of squamous cell carcinoma and
devoid of any gland formation as seen in
adenocarcinoma

55. SMALL CELL LUNG CANCER
 SCLC is characterized by proliferation of
small cells with scant cytoplasm, illdefined
borders, salt and pepper chromatin, frequent
nuclear molding, and a high mitotic count.
 Staining is usually positive for thyroid
transcription factor-1,CD 56, synaptophysin,
and chromogranin.
 Up 98% patients SCLC Hx smoking.

57.  The natu. hx of SCLC early meta. and death.
Unlike NSCLC, SCLC is always
 SCLC shows an excellent response to
chemotherapy, but almost always recurs.

58. Etiology of bronchogenic
carcinoma
 Tobacco smoking More than 85-90% of
lung cancers develop in smokers,
 one in nine smokers develops lung cancer
 The cumulative lung cancer risk among
lifelong heavy smokers can be as high as 30%
compared with a lifetime risk of less than 1%
in nonsmokers

62.  In one study, household exposure of 25 or more
smoker-years before adulthood doubled the risk
for lung cancer.
 exposure of less than 25 smoker-years did not
increase risk.
 At least 17% of lung cancers in nonsmokers are
thought to be attributable to exposure to high
levels of ETS during childhood and adolescence

63. Etiology of bronchogenic
carcinoma
 Other Types of Smoking
 1- Cigar smoking
 associated with increased risk
for lun.Ca, although seemingly
not as great a risk as with
cigarette smoking.
 The tobacco content of cigars
can vary from 1 g to 20 g.
Smoking five cigars a day on
average is equivalent to smoking
one pack of cigarettes a day.

64. Etiology of bronchogenic
carcinoma
 Other Types of Smoking
 2-PIP smoking
 The risk for lung cancer
in pipe smokers is similar
to that in cigar smokers
 Cig.& pip smok. have a
relative risk of lung
cancer of 2.1 to 5.1
compared to nonsmokers

65. Etiology of bronchogenic
carcinoma
 Other Types of Smoking
 3-smoking marijuana and
cocaine
 The effects of them have
not been extensively
studied, and an
association has not been
fully
established between such
inhalant drug use and lung
cancer

66. Etiology of bronchogenic
carcinoma
 Never Smokers < 100 cigarate
 An estimated 15% of lung cancers in men and
up to 53% in women worldwide occur in
never smokers

67. Etiliogy .
clinical and Molecular Characteristics of Lung
Cancer in Smokers and Never Smokers
N.SmokerSmoker
Younger than 60Older than 60Age
Usually femaleUsually maleGender
East asiancaucasianEthnicity
Aden.caALLHistolo.Sub. Tp
EGFR,EML4-ALKKRAS,PIK3CA,RP,P53Asso.mutation/alteration

68. Etiology of bronchogenic
carcinoma
synergestic effect smok.
smoking

69. Etiology of bronchogenic
carcinoma
 lung Scars
Any granulomatouse disease in lung
Fibrosis
scleroderma
Asbestosis

70. Etiliogy …..
 Genetic Factors
 Familial aggregation of cases has also been
documented.
 In a case control study conducted at the author’s
institute, patients with lung cancer were more likely
than controls to have relatives with cancers

71. Etiliogy …..
 Genetic Factors
 Cassidy et al.
 also highlighted a significantly increased risk
for lung cancer specifically for persons with a
family history of early-onset lung cancer(<60
years of age)

72. Etiliogy …..
 Gender
 In the late 1980s, lung cancer surpassed breast
cancer as the leading cause of cancer death in
women
 Since 1950 there has been a more than 600%
increase in the lung cancer mortality rate in women.
 lung cancer in never smoking women is more
common than in never smoking men

73. Etiliogy …..
 Gender
 The gender differences in susceptibility may be
related to differences in nicotine metabolism and in
metabolic activation or detoxification of lung
carcinogens;
 women have higher levels of DNA adducts than
men, which may result in greater susceptibility to
carcinogens.

74. Etiliogy …..
 Gender
 Hormonal factors may also play a role in
susceptibility.
 A case-control study showed that estrogen
replacement therapy was significantly associated
with an increased risk for adenocarcinoma(odds ratio
1.7), and the combination of cigarette smoking and
estrogen replacement increased that risk substantially
(odds ratio 32.4)
 Conversely, early menopause (age 40 years or
younger) was associated with a decreased risk for
adenocarcinoma

75. Etiliogy …..
 Race and ethnicity
 the incidence of lung cancer is substantially higher
among blacks
 and lower among Japanese Americans and Hispanics
than among whites in the United States
 These differences initially have been attributed to
the variations in cigarette smoking pattern
 The explanation for these racial or ethnic variations
in risk for lung cancer is not known.
 Black Americans also have higher mortality rates
from lung cancer than white Americans

76. Etiliogy …..
 Age
 Although smoking prevalence is lowest among
persons aged 65 years and older (9.3%)
 More than 65% of patients with lung cancer are older
than 65 years
 The mean age at the time of diagnosis is 71 years
old

77. Etiliogy …..

78. Etiliogy …..
 Diet and obesity
 It has been suggested that diet is responsible for
approximately 30%of all cancers.
 For example, low serum concentrations of antioxidants,such
as vitamins A, C, and E, have been associated with the
development of lung cancer.
 several large intervention trials have been conducted to
examine the relationship. found that vitamin
supplementation did not reduce lung cancer risk, and in some
circumstances, actually increased the incidence of lung
cancer. Therefore, the use of supplemental β-carotene and
vitamin A is discouraged

79. Etiliogy …..
 Other lung disease
 COPD
 Study (evaluated 602 patients with L.CA)
 50% of them had prebronchodilator pulmonary function test
results consistent with a diagnosis of COPD GOLD stage 2
and higher, independent of age, sex, and smoking history,
with an odds ratio of 11.6
 The prevalence of COPD in patients with newly diagnosed
lung cancer was six fold greater than matched smokers
 COPD,CRP & HIGH DOSE INHALED STEROID.

80. Etiliogy …..
 Infection
 Oncogenic viruses
 HPV DNA has been detected in lung squamous cell
carcinoma tissues.
 (EBV) which is associated with Burkitt lymphoma and
nasopharyngeal carcinoma, has been strongly associated
with lymphoepithelioma like carcinoma (LELC), a rare form
of lung cancer in Asian patients.
 Chlamydia pneumoniae
 Pulmonary tuberculosis
 HIV.


81. Electrical smoking
 An electronic cigarette
is a battery-operated
device that emits
doses of vaporized
nicotine, or non-
nicotine solutions, for
the user to inhale.

86. Here are some key points about e-cigarettes.
 E-cigarettes aim to resemble cigarettes, but without burning
tobacco.
 They are sold as aids to reduce or quit smoking, and some
people find them helpful for this.
 However, research shows that they may have a negative
impact on health.
 Health authorities are trying to tighten up regulations to
discourage young people from using e-cigarettes.

88. Clinical pictures
 Clinical features:
 • Major complaints are
 - Cough (50-75%),
 - Weight loss (40%),
 - Chest pain (40%),
 - Dyspnea (20%) and
 - Haemoptysis.

89. pulmonary
 Cough 75% of SCC & SCLC Any new
variant cough in smoker Ix
 Haemoptysise which is coug.blood ,asphyxia
 Its more in central lesion
 Chest pain more in young ,usually dull ache pain.

90. pulmonary
 Dyspnea .by itself not cause dysp.but indirectly by
causing pneu.atelac.ple.effu.,pneum.&lym.spread
 Hoarseness of voice/ LN involvment
 Pleu.eff.may be serous,serosangeose and bloody
Bloody .indicate MGNT effus.
Benign may 2nd.pneumnities,atel,or lymphatic spre.

91. pulmonary
 SVCO
 (SVC) vulnerable to
extrinsic compression .
 The thin vessel wall
coupled with low
intravascular pressure
and surr. LN
 Ca bron. 46 to 75% of
all cases of SVC

92.  Svco .
 SVC obstruction may get complicated
with jugular venous and
cerebrovascular thrombosis
Pulmonary
facial edema
prominent veins
SCLC>NSCLC
Stent
Radiotherapy
Chemothereapy

93.  Pancoats tumor
thoracic outlet syndrome
Horner syndrome
Miosis
Anhydrosis
Ptosis
MAP
NSCLC

94. Paranewplastic

95.  A 62-y. man 6-week hx cough, hemoptysis,
and SOB.
 Prior to this, he reports feeling well except for
some difficulty rising out of a chair.
 Hx 50-pac-y,no PMHx & no medications.
 O/E,vital N., SPo2 90%; BMI is 30.
 CV and chest exam. are unremarkable.
 Neur. Ex., symme. proxi. muscle weakness in
UL&LL.
 There is no LAP,CXR Rt hil.mass CT 8 CM
hil.mass adjacent to the mediastinum with bulky
bilateral mediastinal lymphadenopathy.

96. Which of the following is the
most likely diagnosis?
A Adenocarcinoma of the lung
B Atypical bronchial carcinoid tumor
C Small cell lung cancer
D Squamous cell carcinoma of the lung

97. Which of the following is the
most likely diagnosis?
A Adenocarcinoma of the lung
B Atypical bronchial carcinoid tumor
C Small cell lung cancer
D Squamous cell carcinoma of the lung

99.  Hypertrophic pulmonary osteoarthropathy
(HPOA).
 clubbing
 This is a tender painful periostitis of the distal
end of bones
 arthralgia
 X-rays reveal subperiosteal new bone
formation.
 SCC

100. Paranewplastic syndrome
Hypercalcemia(SCC) ,PTHrP, cytokines,metas.
poor progn.
Usually indicate stage 3 or 4
 SIADH (SCLC), hypo Na. cerebral edema,
Patient suffer from anorexia ,nausea &vomiting
usually seen after starting chemo.

101.  Cushing syndrome
 Ectopic adrenocorticotrophic hormone
secretion
 SCLC

102. Paranewplastic syndrome

103. Paranewplastic syndrome
Eatn lambort syndrome

104. Feature 2ndary to metastasis
>AD

105. Diagnosis

106. Diagnosis
The main aims of investigation are
1-to confirm the diagnosis,
2-establish the histological cell type
3-define the extent of the disease.
IX
1-Ix to confirm disease
2-Ix to assess the stage
3-Ix to assess fitness for the treatment

107. Establishing a Diagnosis
 For the lesions with
 lower likelihood of malignancy, a tissue
diagnosis can be pursued with sputum
cytology or bronchoscopy if the lesion is
located centrally
 Transthoracic Needle Aspiration (TTNA) if
the lesion is peripheral.

108.  literature, sensi. and spec. of sputum cytology
were 66% and 99%, respectively
 In the same study, sensitivity of FOB
 central tumors 88%, compared with 69% for
peripheral tumors.
 Among the bronchoscopic techniques, endo.
Biop. were associated with high.sen. (74%),
brushings (59%)
and washings (48%).

109.  peripheral lesions >2 cm, TTNA had a
sensitivity of 62% as compared to 33% <2 cm
 Comp. of TTNA
 1-pneumothrax 27%
 2-haemoptesis 5%
 3-local bleeding 11%

110.  Pleu.effusion
 The sensitivity of pleural fluid cytology is
only 60%, which increases to 80% with three
separate fluid specimens and therefore a
minimum of three samples should be
evaluated by an experienced cytologist
 Pleural biopsy is > sensitive

111.  If the lesion is high.suspecious
 The mentioned modalities are useful in
confirming the diagnosis, the false-negative
rate for all three has not been well defined, or
remains too high to rule out the diagnosis
effectively
 Autofluorescence Bronchoscopy (AFB) and
electromagnetic navigation.

113. Diagnosis
imaging

121. IMMUNOHISTOCHEMISTRY
1-IHC may be used to verify neuroendcrine
diferentiation within a tumor
 neuron-specific enolase (NSE), CD56 or
NCAM, synaptophysin, chromogranin, and
Leu7.
 2-in diferentiating primary from metastatic
AD
 thyroid transcription factor-1 ( TTF-1)

122. IMMUNOHISTOCHEMISTRY
3-in diferentiating different hist.type within
lung
AD +NAP,+TTF1
SCC - NAP,-TTF1
SCLC -NAP,+TTF1

124. Molecular biology terminology
Onco-gene:
“A gene that is a mutated (changed) form of a gene involved in
normal cell growth”
Tumor suppressor gene:
“A type of gene that makes a protein called a tumor suppressor
protein that helps control cell growth. Also called anti-oncogene”

125. MOLECULAR BIOLOGY
 Several genetic alterations have been observed in
lung cancer
 The main molecular mechanisms observed in its
pathogenesis include
1-abnormalities in growth-stimulatory signaling
pathways,
2-abnormalities in tumor suppressor gene
pathways,
3-evasion of apoptosis
4- epigenetic changes

132. KRAS
Most common
mutation: ~25% of all
adenocarcinoma
Exclusive to smoker
Mutation has lack of
therapeutic
efficacy shorter
survival
No targeted therapy
established so far
Non-Small Cell Lung Cancer, NCCN Guidelines Version7.2015
https://sangakukan.jp/journal/journal_contents/2013/01/articles/-1301
02-1/1301-02-
1_tmlh.eiclrtea

133. EGFR
Mutation cause receptor
deregulation or over
expression
Overall frequencies in
NSCLC = 10-15%
Most common forms:
Deletions in exon 19 and
exon 21 [sensitizing EGFR
mutation]
Sensitive to small
molecule tyrosine kinase
inhibitor TKI
Erlotinib, Gefitinib,
Afatnibe
Non-Small Cell Lung Cancer, NCCN Guidelines Version7.2015
Brambilla E. et al. Eur Respir J.2009;33(6):1485–1497
Erlotinib

134. EML4-ALK
Estimates 2-7% of
patients with NSCLC and
common in young men
(median: 52 years)
Due to inversion in
chromosome 2 that links
EML4 to ALK cancer
cell proliferation
Does not occur
concurrently with EGFR or
KRAS
Sensitive to TKI
Crizotinib,ceritnib
Non-Small Cell Lung Cancer, NCCN Guidelines Version7.2015

135.  Genetic mutation testing
,biomarker,moleculartesting
 To perform it the sample is taken ----entire
tumour is removed or part of it is collected
biopsy
 Genetic DNA is then removed from
tum.sample and then tested for gen.mut.
 10-14 test result avail.

136.  If no enough sample. For multiple mutation
 Then it priorised based on
1-which mut.patient may have
2-mut. Most likely to be treatable with aproved
target thearpy –e.g for NSCLC
EGFR &ALK gen.muta.

137. Indica. for ALK &EGFR testing
 1-stage 4 AD ,AD that has returned after
initial Dx of stage1,2,3 LC
 2-Patient with stage1,2,3 AD at the time of
Dx
 3-Dx.ing SCC & SCLC from specimen
comes from small biopsy

151.  patient with CT thorax report :
 "There is a mass arising from the left main
bronchus, 1.5 cm from the carina and not directly
involving the carina. It is causing almost complete
obstruction of the left main bronchus, and is likely
to represent a primary lung tumour.
 There are several left hil. LN, the largest measuring
2 cm. The TNM staging is T3N1MX."

152.  What is the TNM staging
A-T1N1MX
B-T2N1MX
C-T2N2MX
D-T3N1MX
E- T3N2MX

153.  What is the TNM staging
A-T1N1MX
B-T2N1MX
C-T2N2MX
D-T3N1MX
E- T3N2MX

154. Using the above information what is the
staging?
A-IB
B-IIB
C-IIIA
D-IIIB
D-IV

155. Using the above information what is the
staging?
A-IB
B-IIB
C-IIIA
D-IIIB
D-IV

156. Screening and prevention
 The surgeon general first exposed the link
between smoking and lung cancer in a report
that was released in 1964
 Until a former smoker is past fifteen years
smoke-free, they are considered to be at
approximately the same risk factor as patients
who are currently smoking

157. Screening and prevention

159. NCCN and USPSTF
 The National Comprehensive Cancer Network (NCCN) is a
collaboration of twenty-five highly regarded cancer centers
 They routinely issue consensus-based clinical practice
guidelines on how to most effectively diagnose and treat
various forms of cancer
 NCCN has recommended screening for high risk individuals
but only recently has any momentum begun
 The United States Preventative Services Task Force
(USPSTF) helped move the fight forward in July 2013,
endorsing low-dose CT screening for those at the highest risk
of developing lung cancer

160. ELCAP
 The Early Lung Cancer Action Program (ELCAP) is an
organization formed in 1992, consisting of a group of
physicians from Cornell University Medical Center and other
specialists to establish research parameters to positively
impact lung cancer detection
 This design utilized both chest radiography and low-dose
chest CT
 Baseline scanning was established followed by repeat annual
screening
 This research forged the way for others to build upon
 ELCAP was scrutinized for not randomizing the trial

169. Management

173.  treatment For Stage I and II NSCLC is
Surgical resection
 Operative
MR patients rese. by thoracic or
cardiothoracic than those removed by general
surgeons
 SR in patients who undergo resection in a
facilities with a high surgical volume
compared with those performing fewer than
70 procedures per year

176.  In patients with stage IA NSCLC, lobecotomy is
superior to wedge resection with respect to rates of
local recurrence

178.  In patients with co morbidities, compromised
pulmonary reserve & small peripheral lesions
limited resection,wedge resection, and
segmentectomy (potentially by VATS) may be
reasonable surgical option.
 Pneumonectomy is reserved for patients with
central tumors

180.  5-y SR 60–80% I NSCLC
40–50% II NSCLC
 the therapeutic benefit of nodal dissection
versus nodal sampling is contraversial
 A pooled analysis of three trials involving
patients with stages I to IIIA NSCLC
demonstrated a superior 4-year survival in
patients undergoing resection and a complete
mediastinal lymph node dissection compared
with lymph node sampling

181.  Radiation Therapy in Stages I and II NSCLC
 No role for post operative radiation
 I and II disease who either refuse or are not
suitable candidates for surgery should be
considered for radiation therapy with curative
intent .
 (SBRT ) Stereotactic body radiation therapy
is new technique in tre.pulm.nodule (≤5 cm)

182.  studies, disease control rates are >90%, and 5-
y. SR 60% SBRT
 SR range from 13 to 39% in I or II NSCLC
treated with external beam RT
 Cryoablation .used to treat small (≤3 m) little
data exist on long-term outcomes with this
technique.

183. Chemotherapy in Stages I and II
NSCLC
 a landmark MA of cisplatin-based adjuvant
chemotherapy trials in patients with resected
stages I to IIIA NSCLC (the Lung Adjuvant
Cisplatin Evaluation [LACE] Study)
demonstrated a 5.4% improve. in 5-SR for
ACT compared to surgery alone, SR benefit
was seemingly confined to II or III
 survival was worsened in IA with ACT
 IB, there was a modest improvement in
survival of questionable clinical significance.

185.  ACT was also detrimental in patients with poor
performance status (Eastern Cooperative
Oncology Group [ECOG] performance status =
2)
 data suggest ACT is best applied in patients
with res. stage II or III NSCLC
 There is no apparent role for ACT in patients
with rese. stage IA or IB NSCLC
 exception is the stage IB patient with a rese.
lesion ≥4 cm

187.  If a decision is made to proceed with ACT,,
treatment should be initiated 6–12 weeks after
surgery, assuming the patient has fully
recovered,
 administered for no more than 4 cycles
 cisplatin-based CTH is preferred treatment
regimen
 carboplatin can be substituted
 Platinum plus vinorelbine is most commonly
used

188. NACT
 With the exception superior sulcus tumors,
the role of NACT in stage I to III disease is
not welldefined
 However, a MA 15 randomized controlled
trials involving more than 2300 patients with
stage I to III NSCLC
 suggested 5-year survival benefit (i e , ~5%)
that is virtually identical to the survival
benefit achieved with postoperative chemo
therapy

189.  patients with resected NSCLC are at high risk
recurrence, 18–24 months of surgery
 Based on the timing of most recurrences,
some guidelines recommend a C CT 6
months for the first 3 years after surgery,
followed by yearly CT scans without contrast
thereafter.

190. MANAGEMENT OF STAGE III
NSCLC
 Management patients usually requires a
combined-modality
 Many aspects of therapy patients with stage
III NSCLC remain controversial, and the
optimal treatment strategy has not been
clearly defined

191. Role of the traditional treatment modalities in
different stages of non-small cell lung cancer
RadiotherapyChemotherapySurgeryStage*
Yes (post-operative)Yes(adjuvant or
neoadjuvant)
YesIIIA (non-
bulky)
Yes (sequential or
concurrent)
YesNot routinelyIIIA (bulky)
Yes (sequential or
concurrent)
YesNoIIIB (without
pleural
effusion)
Only for palliationYesNoIIIB (with
pleural
effusion)and IV

192.  E.g patients with limited stage IIIA disease
 where involved mediastinal lymph nodes can be
completed resected, initial surgery followed by post
operative CHT (with or without RT)
 patients with Clinically evident bulky mediastinal
LN, treatment is concurrent CRT , in some cases,
the latter group patients may be candidates for
surgery following CRT

193.  Superior Sulcus Tumors (Pancoast Tumors)
 distinctive subset stage III disease
 tumors should undergo the same staging
procedures as all patients with stage II and III
NSCLC
 NAC or combined CRT followed by surgery is
reserved for those without N2 involvement. This
approach yields excellent survival out comes
(>50% 5-year survival )

194.  Patients with N2 disease are less likely to
benefit from surgery and can be managed
with CRT alone
 Patients presenting with metast. disease can
be treated with RT (with or without CTH.) for
symptom palliation

195. MANAGEMENT OF
METASTATIC
 NSCLC 40% IV disease
 median SR (4–6 m ) and a 1-year survival 10%
when managed with BSC alone
 signif. Num. patients who 1st presented with
early stage NSCLC will eventually relapse with
distant disease
 Patients who have recur.disease have a better
prognosis than those presenting with meta.
disease at the time diagnosis quality

196.  Standard medical management, the judicious
use of pain medications, and use RT and CTH
forms the cornerstone of mang.
 CTH palliates symptoms, improves the life,
and improves survival in patients with stage
IV NSCLC, particularly in patients with good
performance status.

197.  optimal CTH regimen for advanced NSCLC
 majority randomized trials showed no major
survival improvement with any one regimen
versus another
 An ongoing debate about duration of
platinum-based CTH
 large phase III randomized trials have failed
to show benefit for increasing the duration of
platinum-based doublet CTH beyond 4to6
cycle

198.  longer duration CTH has been associated with
increased toxicities and impaired quality of
life

199. Maintenance therapy following initial platinum
based therapy
 in a landmark randomized phase III trial,
patients with
 non SCC were found to have an improved
survival when treated with cisplatin and
pemetrexed
 By contrast, patients with squamous
 carcinoma had an improved survival when
treated with cisplatin and gemcitabine

200. Target therapy
 Targeted therapy is a class of drug, it stops
the action of molecules that are key to the
growth of cancer cells. so not like
chemotherapy it affects cancer cells more
than normal cells.

201. FDA approved specific targeted therapies
Erlotinib: EGFR positive mutation
Crizotinib: EML4-ALK positive mutation
Bevacizumab*: if neither positive

202.  Bevacizumab, MC Ab against VEGF
 improve response rate, progression-free
survival, and overall survival in patients with
advanced disease when combined with CTH
 However, bevacizumab cannot be given to
patients with SCC because their tendency to
experience serious hemorrhagi efects

204.  currently carboplatin/paclitaxel and
bevacizumab or carboplatin/pemetrexed and
bevacizumab are appropriate regimens for
first-line treatment for stage IV nonsquamus
NSCLC patients

206. Erlotinib (Tarceva ®(
Small molecule TKI used as:
First-line: patient with EGFR mutation
Second line: locally advanced/metastatic
NSCLC after progression on at least one prior
chemotherapy
Dose: 150 mg by mouth daily until disease
progression or unacceptable toxicity
Drug-drug interaction: strong CYP3A4
(inducers/inhibitors); proton pump inhibitors

208. Side effects:
Dermatologic: skin rash (49% to 85%; grade 3:
 5% to 13%; grade 4: <1%; median onset: 8 days)
Gastrointestinal: diarrhea (20% to 62%; grade
3: 2% to 6%; grade 4: <1%; median onset: 12
days)
Respiratory: Cough (33% to 48%), dyspnea
 (41% to 45%; grades 3/4: 8% to 28%

209. Dose Adjustments: Toxicity
Discontinuation of therapy:
Bullous, blister or exfoliative
GI perforation
Corneal perforation or severe ulceration
Withhold and reinitiate with 50 mg dose
reduction:
Severe rash
Dehydration due to diarrhea
Acute or worsening ocular toxicities or keratitis

210. Landmark Trials
Trial Study Design
Patient
Population
Results
OPTIMAL n
=83
Multicenter, open-label,
randomized, phase III. Oral
erlotinib (150mg/d) vs.
chemotherapy (GEM+CIS)
Adults >18years
with confirmed
Stage IIIB or IV
NSCLC+
EGFR positive
mutation
Median progression-free survival (PFS):
13.1months vs.4.6
months; p<0.0001. Grade3and4side
effects were less in erlotinib group
EURTAC n
=174
Multicenter, multinational,
open- label, randomized,
phase III. Oral erlotinib (150
mg/d) vs. chemo (DTX+CIS)
Adults >18years
with confirmed
Stage IIIB or IV
NSCLC+
EGFR positive
mutation
Median PFS:9.7months vs.5.2
months; p<0.0001. Grade3&4hematologic
toxicity was higher in chemo group (22%vs.
none), whereas, erlotinib has higher rash
(13%), and ↑ of LFTs (2%)

213. Crizotinib (Xalkori ®)
Small molecule tyrosine kinase inhibitor of c-MET, ALK, or ROS 1
and indicated for:
ALK-positive metastatic NSCLC
Dose: 250 mg orally twice daily, continue treatment until disease
progression or unacceptable toxicity
Drug-drug interaction: strong CYP3A4 inhibitors/inducers
Ingnateus SH. et al. Drug Design, Development and Therapy
2011:5471–485

214. Side effects:
Cardiovascular: edema (28% to 39%), bradycardia (5% to 11%)
Metabolic: hypophosphatemia (28%), hypokalemia (18%)
Gastrointestinal: Diarrhea (43% to 60%), nausea (51% to 55%),
 vomiting (40% to 47%)
Hematologic: lymphocytopenia (51%; grades 3/4: 9% to 11%),
 neutropenia (49%; grades 3/4: 5% to 12%)
Hepatic: Increased serum ALT (13% to 76%; grades 3/4: 5%
to17%), AST (9% to 61%; grades 3/4: 2% to 9%)
Ophthalmic: Visual disturbance (55% to 62%; onset: <2 weeks)

215. Dose Adjustments: Toxicity
Discontinuation of therapy:
Pulmonary toxicity: Interstitial lung disease (any grade)
Grade 4 hematologic toxicity despite lowest dose (250
mg once daily)
QTc >500 msec or ≥60 msec change from baseline with
life-threatening symptoms
Erlotinib. Lexi-Drugs Multinational [Internet]. Accessed: June 062015

216. Dose reduction necessary, if patient develops grade 3
or 4 cardiac, hematologic, and hepatotoxicity
Dose reduction scheme:
 Step1: reduce dose to 200 mg orally twice daily; if not
 tolerable
 Step2: reduce to 250 mg once daily. If not tolerable
 Step3: reduce to 250 mg once daily

223.  A randomized phase III trial in SCLC is
underway To validate these data