A CaseA Case

Mr. G61 y/o male transferred from OSH for

weakness, HAHad abnormal imaging discovered at OSHSx’s present for ~3-4 monthsWhat else do you want to know?

Case continuedCase 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 continuedCase 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 continuedCase continued

PMH – migraines, depression, DLDSocial – 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…

Case continuedCase 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 continuedCase 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 continuedCase continued

Work-up includes: Labs

Na K Cl CO2 BUN Cr Glu Ca

137 4.6 105 23 21 0.83 146 9.9

TP Alb TB AP AST ALT

7.6 4.4 0.6 100 18 17

WBC Hgb Hct Plt

7.4 16.8 47.7 246

Case continuedCase 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 continuedCase 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 continuedCase continued

Next step?Treat the acute process

– Steroids: Decadron 6mg Q6h– SSI– Neuro following

So what about that CXR?

Case continuedCase 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 continuedCase continued

A diagnostic test was performedBronch showed:

– Negative endobronchial bx– BAL negative for malignant cells– Subcarinal LN bx: non-small cell lung ca

Case continuedCase 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 continuedCase continued

Three months later pt admitted for worsening fatigue/weakness

Hospice services initiated and patient passed away 9 days later

Lung CancerLung Cancer

Matthew Knoch

Senior Talk

May 20th and 22nd, 2009

University Hospitals Case Medical Center and VA, Cleveland OH

ObjectivesObjectives

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 InformationBackground 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 Background Information (Cont)(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 Background Information (Cont)(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?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 thereIt 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 Why are cigarettes so bad and how do they cause cancer?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 ResponseMore 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: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 Cigarette Consumption, per capita in adultscapita in adults

More good news…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 FactorsOther Risk Factors Industrial – 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%

Molecular GeneticsMolecular 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 implicatedOther factors implicated

Scarring – researchers have noted cancer formation in the region of prior lung scarring– These include areas of old infarct, metallic

foreign bodies, wounds and granulomatous infections

– Most of these cancers are histiologically adenocarcinomas

Types Of Lung CancerTypes Of Lung Cancer

Squamous cell – 25-40%, epidermoid derived

Adenocarcinoma – 25-40%, bronchial, acinar, papillary, solid, broncioalveolar

Small cell – 20-25%, oat, intermediate cellLarge cell – 10-15%, undifferentiated, giant

or clear cell Combined – squamous and adenocarcinoma

So what about gender?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 NewsGood News

The most important risk factors implicated in lung cancer are modifiable, e.g. stop smoking

Mechanism of cancer Mechanism of cancer formationformation

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 likesWhat lung cancer likes

Adrenals - ~50% of cancersLiver – 30-50%Brain – 20%Bone – 20%

AdenocarcinomaAdenocarcinoma

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 CaSquamous Cell Ca

More often found in men, usually associated with long smoking history

Centrally located lesions and spread locallyLater metasteses

Small Cell CaSmall Cell Ca

Oat cell’s given small histologic appearanceHigh neuroendocrine activity:

– PTH-like peptides– Neuron-specific enolase

Strongly associated with Tob exposureCentrally located

Large Cell CaLarge Cell Ca

Likely represent squamous cell and adenocarcinomas that are undifferentiated

Complications of Lung CaComplications of Lung Ca

Obstruction – emphysema vs. atelectasisPNA – abscess formationSVC syndromePericarditisPleuritisNeuroendocrine abnormalitiesHypercoagulable states

DiagnosisDiagnosis

Start with H&PIllicit good history, especially social

including exposure risks– Cough, hemoptysis, weight loss, chest pain,

SOB

Physical exam

DiagnosisDiagnosis

CXR – identifies nodules usually >1cmCT Chest – more definitive view of lung

parenchyma and adjacent lymph nodesPET scan – helpful in staging to determine

degree of metastases MRI/CT brain – useful in looking at CNS

involvement

DifferentialDifferential

Other than cancer: – TB– PE– MI– Other lung pathology: PTX– Simple PNA’s– Sarcoid

Symptoms of Lung CaSymptoms of Lung Ca

PNA Effusions Hoarseness/dysphagia SOB, diaphragm paralysis, chest pain, rib

involvement SVC Syndrome Horner’s Syndrome – Pancoast tumors Pericarditis/tamponade

Paraneoplastic syndromesParaneoplastic syndromes

SIADH – small cellACTH-producing tumors – small cellPTH/PTH-rp – squamous cellCalcitoninGonadotropinSerotoninLambert-Eaton syndrome – small cell

Work-upWork-up

If cancer is the answer, tissue is the issue– i.e. bronch vs. VATS vs. CT-guided bx or

peripheral bx

Staging - TNMStaging - 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 - TNMStaging - TNM

Lymph Node– N0 = no involvement– N1 = hilar nodes– N2 = mediastinal nodes– N3 = contralateral nodes or ipsilateral

supraclavicular (nonresectable)

Staging - TNMStaging - TNM

Metastases– M0 = none– M1 = presence (nonresectable)

Staging ContinuedStaging Continued

Stage IA - T1 N0 M0Stage IB - T2 N0 M0 (T > 3cm)

Staging ContinuedStaging ContinuedStage IIA - T1 N1 M0

Stage IIB - T2 N1 M0

T3 N0 M0

Staging ContinuedStaging ContinuedStage IIIA - T3 N1 M0

T1-3 N2 M0

Stage IIIB - Any T N3 M0

T4 Any N M0

Staging ContinuedStaging ContinuedStage IV - Any T Any N M1

Treatment OptionsTreatment 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 SurgeryContraindications 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

PrognosisPrognosis

Year ofDiagnosis

All Races Whites Blacks

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

5-Year Relative Survival Rates by Year of Diagnosis

ConclusionsConclusions 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

ConclusionsConclusions

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

Thank YouThank You

Questions?Food for thought:

“If you want to smoke

something, smoke a

banana”

ReferencesReferences

Cotran, Kumar, Collins. Robbins Pathologic Basis of Disease. 6th edition, pages 741-753.

American Cancer Society – www.cancer.org Uptodate George, Light, Matthay, Matthay. Chest Medicine

– Essentials of Pulmonary and Critical Care Medicine, pages 316-344.

Carpenter, Griggs, Loscalzo. Cecil Essentials of Medicine, 6th edition, pages 213-221.