Download Lung Cancer

A Case
 Mr.
G
 61 y/o male transferred from OSH for
weakness, HA
 Had abnormal imaging discovered at OSH
 Sx’s present for ~3-4 months
 What else do you want to know?
Case continued
 HA’s
occur 3-4 times/day, lasting 10-15
minutes with a black spot in the center of his
R eye visual field
 Was seen 2 months earlier in UCC,
evaluated by neuro who recommended MRI,
scheduled 11 days from now
Case continued
 Notes
LUE weakness, intermittently
dropping objects
 Intermittent LLE weakness and increased
sense of smell
 Remainder of ROS unremarkable except for
some mild increased SOB
 Next?
Case continued
– migraines, depression, DLD
 Social – handyman, former factory worker,
remote EtOH (16 years ago), 1.5-2 ppd with
80 pack year hx
 Medications – combivent, metoprolol,
simvastatin, ASA, omeprazole, naproxen
 After history comes…
 PMH
Case continued
 Physical
exam
 97.2 – 88 – 20 – 138/82 – 95% RA
 GEN: Alert, intermittent confusion
 HEENT: NC/AT, PERRLA, EOMI, MMM
 RESP: CTAB, occ wheeze
 CVS: RRR No g/m/r
 ABD: Soft. NT/ND +BS
 EXT:Warm, well-perfused. No c/c/e
Case continued
 NEURO:Grossly
non-focal with good motor
strength bilaterally in upper and lower
extremities. Sensation intact. Noted to have
transient weakness/instability on ambulation
by nursing staff.
 Now what?
Case continued
Work-up
includes:
Labs
Na
K
137 4.6
TP
7.6
WBC
7.4
Cl
105
Alb
4.4
Hgb
16.8
CO2 BUN Cr
23
21
0.83
TB
0.6
AP
100
Hct
47.7
AST
18
Plt
246
Glu
146
ALT
17
Ca
9.9
Case continued
Imaging
as follows:
CT head - at least two mass lesions in the right
cerebral hemisphere resulting in extensive right
cerebral edema and leftward subfalcine shift and
ventricular effacement. There is sulcal effacement as
well. No uncal herniation is identified. There is no
associated hemorrhage."
Also noted mass lesion posterior in the left parietal
lobe w/ ass’d edema
Case continued
 MRI
- Multiple supratentorial metastatic
lesions with the largest lesion in the right
parietal lobe with mass-effect and midline
shift of 1 cm. Focal area of chronic ischemic
change/gliosis in the right cerebellar
hemisphere
Case continued
 Next
step?
 Treat the acute process
–Steroids: Decadron 6mg Q6h
–SSI
–Neuro following
So what about that CXR?
Case continued
 CXR
- Right hilar soft tissue fullness, recommend
CT chest as well as chronic appearing coarse
interstitial densities in the lungs are likely reflecting
sequela from smoking and/or emphysema
 CT Chest - Subcarinal and right hilar adenopathy
with maximal diameter of 2.3 cm associated with
several right lung nodules
 CT Abd/pelv – unremarkable
Case continued
 A diagnostic
test was performed
 Bronch showed:
– Negative endobronchial bx
– BAL negative for malignant cells
– Subcarinal LN bx: non-small cell lung ca
Case continued
 Pt
discharged after acute process resolved and was
seen by H/O in f/u – completed course of radiation
therapy to brain and initiated on Tarceva
 T1N1M1 = stage IV
 Despite therapy had progression of disease so was
initiated on carbo/taxol therapy
 Repeat MRI showed worsening cerebral edema
Case continued
 Three
months later pt admitted for
worsening fatigue/weakness
 Hospice services initiated and patient passed
away 9 days later
Lung Cancer
Matthew Knoch
Senior Talk
May 20th and 22nd, 2009
University Hospitals Case Medical Center and VA,
Cleveland OH
Objectives
 Identify
background knowledge of lung
cancer rates and incidence, including
etiology and causal factors
 Learn the different types of lung
malignancies and understand their diagnosis,
staging and prognosis
 Understand the basic treatment options
Background Information
 Most
common type of cancer in industrialized
nations – leading cause of mortality from cancer
 Accounts for 13% of all new cancer diagnoses and
30% of cancer deaths in men and 7% of deaths
among both sexes however incidence in women is
increasing greatly
 Remains the most frequent fatal malignancy, ~91K
male and ~71K female deaths/year
Background Information (Cont)
 Annual
deaths have increased from 18,000 in 1950 to
158,000 in 1997 in US and roughly 900,000 deaths
worldwide with >50% of those in developed countries
 Death rate has also increased 3-fold from 19.9 to 74 per
100,000 in men and 7-fold 4.5 to 31 per 100,000 in women
during same time period
 Spectrum of disease – more deaths than the next 3 most
common cancers combined (colon/rectum, breast and
prostate) – 114,690 cases/90,810 deaths in men and 182,460
cases/71,030 deaths in women in 2008
Background Information (Cont)
 Accounts
for 13% of all malignancies in
both sexes
 Most often occurs between ages 40-70,
peaks in the 50-60 age range
So what causes lung cancer?
Probably multifactorial (genetics?)
Not the Only cause (90% of
cases)…but also based upon:
1. Amount of daily smoking
2. Tendency to inhale
3. Duration of smoking
4. Age of initiation of smoking?
Increases risk by about 10-20 fold
over non-smokers in
retrospective studies compared
with control subjects, shown by
landmark epidemiologic studies
in the 1950’s in US/Britain
It doesn’t stop there
Cancers
of the lip, tongue, oropharynx,
throat, bladder and kidney cancer are all
implicated in smoking
So what helps?
• Smoking cessation 10 years out returns risk
level to that of nonsmokers (dose response
relationship exists)
Why are cigarettes so bad and how
do they cause cancer?
 Over
1200 chemical substances (50
identifiable carcinogens) found in the smoke
of cigarettes including:
– Initiators such as PAH
– Promoters such as phenol derivatives
– Radioactive elements: polonium-210, carbon-14,
potassium-40
– Others: arsenic, nickel, molds, additives
More on Dose Response
 The
Cancer Prevention Study II (CPSII)
followed >1,000,000 smokers for 6 years
and found that:
– 1 ppd = 22x the risk of dying from lung cancer
– 2 ppd = 45x the risk of dying from lung cancer
Also helpful, kind of:
 At
least in the US: public health
interventions, litigation and education have
contributed to a decline in smoking and
therefore lung cancer rates, however this is
not the case in developing nations across the
globe
 Roughly 20-25% of the American
population continues to smoke
Cigarette Consumption, per capita in
adults

More good news…
 Experiments
have been unsuccessful in
causing lung cancer in laboratory animals
through prolonged exposure to smoke
 On the other hand, bronchioloalveolar
cancers have been demonstrated but these
are not seen very often in human smokers
Other Risk Factors
– radiation exposure, asbestos, workers exposed to
nickel/chromate/coal/ mustard gas/arsenic/berylium/iron/gold/
haloether and newspaper industry workers (9-15%)
 Air pollution – both indoor and outdoor (1-2%), radon (10%),
difficult to determine though
 Second hand smoke: nonsmoking women married to smokers
had a 1.2x risk of developing cancer – possible
hormonal/metabolism effects, even higher if >2 ppd (roughly
3000 case/year)
 Combined risk factors approach 100%
 Industrial
Molecular Genetics
 So
what does the cumulative effect of all of
these risk factors mean?
– It is thought that by the time a tumor in the lung
has developed that anywhere from 10 to 20
genetic mutations have occurred before a tumor
develops
– These include c-myc, K-ras and p53
Other factors implicated
– researchers have noted cancer
formation in the region of prior lung scarring
 Scarring
– These include areas of old infarct, metallic
foreign bodies, wounds and granulomatous
infections
– Most of these cancers are histiologically
adenocarcinomas
Types Of Lung Cancer
cell – 25-40%, epidermoid derived
Adenocarcinoma – 25-40%, bronchial, acinar,
papillary, solid, broncioalveolar
Small cell – 20-25%, oat, intermediate cell
Large cell – 10-15%, undifferentiated, giant or
clear cell
Combined – squamous and adenocarcinoma
Squamous
So what about gender?
 Since
the 1950’s, a >500% lung cancer
mortality has been identified in women
 Partially due to increasing number of
women smokers, but it has also been
observed that dose for dose women have
increased susceptibility to carcinogen
exposure than men
Good News
 The
most important risk factors implicated
in lung cancer are modifiable, e.g. stop
smoking
Mechanism of cancer formation
 Begins
as in situ cytologic atypia that multiplies
into tumor formation
 May progress into the lumen, spread to adjacent
areas of carina or mediastinum with nodal
involvement, pleural invasion
 Intraparenchymal mass formation
 Rapid growth may cause local obstruction,
hemorrhage or necrosis depending on rate of
growth and location
What lung cancer likes
 Adrenals
- ~50% of cancers
 Liver – 30-50%
 Brain – 20%
 Bone – 20%
Adenocarcinoma
 Includes
bronchial-derived and
bronchioloalveolar, 80% contain mucin
 Incidence greatly increased in the past 20
years
 Most common form in women, probably in
men too; being seen more in smokers
 Cause for the increase? Perhaps related to
addition of filters and deeper inhalation
Squamous Cell Ca
 More
often found in men, usually associated
with long smoking history
 Centrally located lesions and spread locally
 Later metasteses
Small Cell Ca
 Oat
cell’s given small histologic appearance
 High neuroendocrine activity:
– PTH-like peptides
– Neuron-specific enolase
 Strongly
associated with Tob exposure
 Centrally located
Large Cell Ca
Likely
represent squamous cell and
adenocarcinomas that are undifferentiated
Complications of Lung Ca
– emphysema vs. atelectasis
 PNA – abscess formation
 SVC syndrome
 Pericarditis
 Pleuritis
 Neuroendocrine abnormalities
 Hypercoagulable states
 Obstruction
Diagnosis
 Start
with H&P
 Illicit good history, especially social
including exposure risks
– Cough, hemoptysis, weight loss, chest pain, SOB
 Physical
exam
Diagnosis
– identifies nodules usually >1cm
 CT Chest – more definitive view of lung
parenchyma and adjacent lymph nodes
 PET scan – helpful in staging to determine
degree of metastases
 MRI/CT brain – useful in looking at CNS
involvement
 CXR
Differential
 Other
than cancer:
– TB
– PE
– MI
– Other lung pathology: PTX
– Simple PNA’s
– Sarcoid
Symptoms of Lung Ca
 PNA
 Effusions
 Hoarseness/dysphagia
 SOB,
diaphragm paralysis, chest pain, rib
involvement
 SVC Syndrome
 Horner’s Syndrome – Pancoast tumors
 Pericarditis/tamponade
Paraneoplastic syndromes
– small cell
 ACTH-producing tumors – small cell
 PTH/PTH-rp – squamous cell
 Calcitonin
 Gonadotropin
 Serotonin
 Lambert-Eaton syndrome – small cell
 SIADH
Work-up
 If
cancer is the answer, tissue is the issue
–i.e. bronch vs. VATS vs. CT-guided bx or peripheral
bx
Staging - TNM
 Tumor
size:
– T1 < or = to 3cm
– T2 > 3cm
– T3 = local extension (parietal pleura, chest wall
or within 2cm of carina)
– T4 = spread to great vessels, trachea,
mediastinum, esophagus or malignant effusion
(nonresectable)
Staging - TNM
 Lymph
Node
– N0 = no involvement
– N1 = hilar nodes
– N2 = mediastinal nodes
– N3 = contralateral nodes or ipsilateral
supraclavicular (nonresectable)
Staging - TNM
 Metastases
– M0 = none
– M1 = presence (nonresectable)
Staging Continued
Stage
IA
Stage IB
- T1 N0 M0
- T2 N0 M0 (T > 3cm)
Staging Continued
Stage
IIA - T1 N1 M0
Stage
IIB - T2 N1 M0
T3 N0 M0
Staging Continued
Stage
IIIA - T3 N1 M0
T1-3 N2 M0
Stage
IIIB - Any T N3 M0
T4 Any N M0
Staging Continued
Stage IV
-
Any T Any N M1
Treatment Options
 Thoracotomy
with resection is the only curative
treatment available
 Surgical options available if NOT a small cell ca
 Chemotherapy (platinum based, topoisomerase and
mitotic inhibitors), radiation and adjuvant debulking
surgery (usually only palliative unless used in
conjunction with curative resection)
Contraindications for Surgery
 MI
within past 3 months, within 6 months only
relative
 Major arrhythmias
 Severe pulmonary HTN
 Pre-op hypoxia
 Pre-op FEV1/FVC < 80%
 Pre-op FEV1 < 1L
 Predictive post-op FEV1 /FVC < 40% OR
FEV1 <1L
Prognosis
5-Year Relative Survival Rates by Year of Diagnosis
All Races
Whites
Blacks
Year of
Diagnosis
Both Sexes
Males
Females
Both Sexes
Males
Females
Both Sexes
Males
Females
1960-1963a
-
-
-
8
7
11
5
5
6
1970-1973a
-
-
-
10
9
14
7
6
10
1975-1977b
12.7
11.5
15.8
12.8
11.5
15.9
11.5
10.8
14.0
1978-1980b
13.3
11.8
16.7
13.4
12.0
16.6
12.1
10.0
18.1
1981-1983b
13.7
12.1
16.9
13.9
12.3
17.1
11.7
10.5
15.1
1984-1986b
13.3
11.6
16.4
13.5
11.7
16.7
11.4
10.7
13.0
1987-1989b
13.5
12.4
15.4
13.8
12.5
15.8
11.2
11.1
11.5
1990-1992b
14.1
12.6
16.3
14.5
13.0
16.6
10.8
9.6
12.8
1993-1995b
14.9
12.9
17.4
15.1
13.1
17.7
13.1
11.6
15.8
1996-1998b
15.2
13.4
17.4
15.4
13.5
17.7
12.7
11.0
15.2
1999-2005b
16.3e
14.0e
18.8e
16.6e
14.4e
19.1e
12.9e
11.1
15.2
Conclusions
 Lung
cancer is a common malignancy in our society
and throughout the world with the overall highest
morbidity/mortality in terms of malignancies that
unfortunately has not seen a significant increase in
survival rates over the past several decades
 Bottom line, the best thing we can do as physicians
to prevent this disease is to promote smoking
cessation
Conclusions
 Finally,
more research needs to be done for
the treatment of lung cancer and perhaps the
development and implementation of a
screening tool for earlier diagnosis and
treatment of the disease