lung cancer.ppt
TRANSCRIPT
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.