Lung Cancer

Epidemiology and risk factors

• Most common cause of cancer-related death for both men and women in U.S.

• Cigarette smoking: 85% of all lung cancers occur in smokers risk proportional to total pack-years: 1 risk after quitting or reducing, but not to baseline (jama 2005:294 1505) squamous & small cell almost exclusively in smokers adenocarcinoma most common type in nonsmokers bronchioalveolar carcinoma associated with females, nonsmokers. EGFR mutations

• Asbestos: when combined with smoking, synergistic I in risk of lung cancer

• Radon: risk to general population unclear

Pathology

• Non-small cell lung cancer (NSCLC): 85% of lung cancers in U.S.

Peripheral: adenocarcinoma, large cell carcinoma Central: squamous cell carcinoma

Bronchioalveolar carcinoma: track along airways, can be multifocal

• Small cell lung cancer (SCLC): 15% of lung cancers in U.S.; typically central

Clinical manifestations

• 10% are asymptomatic at presentation and are detected incidentally by imaging

• Endobronchial growth of 10 tumor: cough, hemoptysis, dyspnea, wheezing, post-

obstructive pneumonia; more common with squamous or small cell (central location)

• Regional spread pleural effusion, pericardial effusion, hoarseness (recurrent laryngeal nerve palsy).

dysphagia (esophageal compression), stridor (tracheal obstruction) Pancoast's syndrome: apical tumor — brachial plexus involvement (C8.T1.T2) -*

Horner's syndrome, shoulder pain, rib destruction, atrophy of hand muscles superior vena cava syndrome: central tumor — SVC compression — dyspnea, headache, facial swelling, venous distention of neck and chest wall

• Extrathoracic metastases: brain, bone, liver, adrenal, skin

• Paraneoplastic syndromes

Endocrine

ACTH (SCLC) - Cushing's syndrome;ADH (SCLC) • SIADH PTH-rP (squamous cell) — hypercalcemia Skeletal: digital clubbing (non-small cell), hypertrophic pulmonary osteoarthropathy (adenocarcinoma) symmetric polyarthritis and proliferative periostitis of long bones Neurologic (usually small cell): Eaton-Lambert, periph. neuropathy, cerebellar degen. Cutaneous: acanthosis nigricans, dermatomyositis

Hematologic: hypercoagulable state (adenocarcinoma), DIC, marantic endocarditis Screening (N£/m 2005.3522714)

• No proven survival benefit to screening CXR or sputum cytology, even in high-risk Pts

• Survival benefit of screening chest CT in observational studies controversial (NEjm

2006:355:1763; jama 2007:297:953); await RCTS

Diagnostic and staging evaluation

• Imaging: CXR. chest CT (include liver and adrenal glands)

• Tissue bronchoscopy (for central lesions) or CT-guided needle biopsy (for peripheral lesions or accessible sites of suspected metastasis) mediastinoscopy (lymph node bx),VATS (eval. of pleura peripheral lesions), thoracentesis (cell block for cytology), or sputum cytology (for central lesions)

Intrathoracic: mediastinoscopy or VATS; thoracentesis if pleural effusion Extrathoracic.

PET scan or integrated PET-CT more Se than CT alone for detecting mediastinal and distant mets as well as bone mets (N£>m 2000:343:254 & 2003:348:2500) brain MRI for all Pts and bone scan for those w localizing sx or lab abnormalities

• PFTs with quantitative V Q if planned treatment includes surgical resection

TNM Staging System for NSCLC

N stage

NO

N1

N2

N3

stage

Definition

no© nodes

ipsilat. hilar

ipsilat mediast

contralat or supraclav.

T1

Tumor <3 cm

IA

HA

T2

Tumor >3 cm

IB

IIB

T3

Direct invasion of chest wall, diaphragm, mediast pleura, pericard.

IIB

IIIA

T4

Malig. pleural effusion; invasion of mediast. heart, great vessels, trachea, carina, esophagus, vertebral body

• Stages I & II: surgical resection + adjuvant chemo for stage IB-II (nejm

2004350:351 & 2005:352:2589); gene expression data identifies early NSCLC w T risk of recurrence that may benefit from more aggressive chemo (nejm 2006:355:570)

• Stage III: optimal combo/sequence of chemo, radiation, & surgery unknown

IIIA has been viewed as potentially resectable and IIIB as unresectable neoadjuvant chemoradiation may convert unresectable -» resectable

• Stage IV: chemotherapy t survival c w best supportive care standard is a platinum-based doublet (eg, carboplatin paclitaxel)

no single regimen proven superior (NEJM 2002:346:92) palliative radiation used to control local symptoms caused by tumor or metastasis solitary brain metastasis: surgical resection - whole brain irradiation may t survival

• Biologic therapy (for stage IIIB IV)

erlotinib (EGFR inhibitor) if progress after chemo T median survival by 2 mos c w supportive care (nejm 2005.353:123); consider targeting to Pts w EGFR mutations (more common in Asians, females, nonsmokers. bronchioalveolar histology) bevacizumab (anti-VEGF mAb) added to chemo T median survival by 2 mos; T risk of bleeding . exclude if brain mcts or squamous cell CA (hemoptysis) (NEJM 200635S:2542)

NSCLC Simplified Staging Schema.Treatment, and 5-y survival

Stage at dx

Definition

Treatment

s-y

1 10%

Isolated lesion

Surgery • chemo

•60%

II 20%

Hilar node spread

Surgery • radiation • chemo

40-50%

IIIA 15%

Mediast spread, but resectable

Neoadjuvant chemotherapy • radiation surgical resection

25-30%

IIIB 15%

Unresectable

Chemotherapy - radiation ; biologic t surgery (selected cases)

10-20%

IV 40%

Metastatic

Chemo : biologic and or supportive care Palliative radiation

• ERCC1 (excision repair cross-complementation group 1) expression may identify Pts who do not respond to cisplatin-based chemo (nqm 2006:355 983)

• Gene expression data may aid in prognosis (nejm 2006.355:570 & 2007:356:11) SCLC Treatment

• SCLC usually disseminated at presentation, but can be very responsive to chemoradiation

• Chemotherapy (platinum • etoposide) is primary treatment modality

• Thoracic radiation added to chemotherapy improves survival in limited stage disease

• Prophylactic cranial irradiation (PCI) improves survival for limited stage disease in complete remission (nejm 1999:341476)

SCLC Staging Schema and Treatment

Stage

% at dx

Definition Treatment

Median survival

Limited

30-40%

Confined to ipsilat homithorax Radiation • w in one radiation port chemotherapy : PCI

1-2 y

Extensive

60-70%

Beyond one radiation port Chemotherapy

-1y

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