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.
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.
4.
5.
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
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
9.
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.
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)
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)
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.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
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.
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.
56.
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
59.
60.
61.
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
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
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.
82.
83.
84.
85.
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.
87.
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
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
98.
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.
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.
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)
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
126.
127.
128.
129.
130.
131.
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
138.
139.
140.
141.
142.
143.
144.
145.
146.
147.
148.
149.
150.
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
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
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
174.
175.
176. In patients with stage IA NSCLC, lobecotomy is
superior to wedge resection with respect to rates of
local recurrence
177.
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
179.
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.
184.
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
186.
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
203.
204. currently carboplatin/paclitaxel and
bevacizumab or carboplatin/pemetrexed and
bevacizumab are appropriate regimens for
first-line treatment for stage IV nonsquamus
NSCLC patients
205.
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
207.
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%)
211.
212.
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
217.
218.
219.
220.
221.
222.
223. A randomized phase III trial in SCLC is
underway To validate these data