Lung Cancer Jamal Turki, M.D

The term lung cancer, or bronchogenic carcinoma, refers to malignancies that originate in the airways or pulmonary parenchyma Lung cancer is among the most common cancers worldwide Lung cancer is the leading cause of cancer-related mortality in both men and women 

Epidemiology In the United States, lung cancer is the second most common cancer, after prostate cancer in men and breast cancer in women, and the most common cause of cancer deaths.

Cancer Deaths in U.S. (2007 American Cancer Society Data) Lung 160,390 Colorectal 52,180 Breast 40,910 Prostate 27,050

RISK FACTORS Smoking  —account for approximately 90 percent of all lung cancers  The risk of developing lung cancer for a current smoker of one pack per day for 40 years is approximately 20 times that of someone who has never smoked prevention :In individuals who do quit smoking, the risk of developing lung cancer gradually falls for about 15 years before it levels off and remains about twice that of someone who never smoked

RISK FACTORS Environmental toxins — These include exposure to second-hand smoke, asbestos, radon, metals (arsenic, chromium, and nickel), ionizing radiation, and polycyclic aromatic hydrocarbons Pulmonary fibrosis — Several studies have shown that the risk for lung cancer is increased about sevenfold patients with pulmonary fibrosis HIV infection — Genetic factors — Genetic factors can affect both the risk for and prognosis Dietary factors — Epidemiologic evidence has suggested that various dietary factors (antioxidants, cruciferous vegetables, phytoestrogens) may reduce the risk of lung cancer

Asbestosis & Lung Cancer (2007 American Cancer Society Data) Prolonged heavy exposure has relative risk between 2 - 10 of causing lung cancer. Peak incidence 15 - 24 years after exposure. Fiber type is important: Crocidolite & amosite > chrysotile & anthophyllite.

SCREENING Guidelines : Annual screening with low-dose computed tomography (LDCT) scanning to patients aged 55 to 74 years and who have at least a 30 pack-year smoking history and either continue to smoke or have quit within the past 15 years.

PATHOLOGY Adenocarcinoma :40 % , Non-smokers Peripheral, Preexisting scars, Bronchoalv. Squamous cell carcinoma- 25%, smokers, central, Hypercalcemia, cavitation Large cell carcinoma: 5 % Small cell carcinoma: 15 % Others 15%

CLINICAL MANIFESTATIONS Persons aged 50-70 years.  Lung cancer is more common in men than in women. Symptoms may result from local effects of the tumor, from regional or distant spread, or from distant effects not related to metastases (paraneoplastic syndromes). Approximately three-fourths of patients have one or more symptoms at the time of diagnosis.

Cough  — Cough is present in 50 to 75 percent of lung cancer patients at presentation  Squamous cell and small cell carcinomas Bronchorrhea Post-obstructive pneumonia bronchiectasis is uncommon 

Hemoptysis : 25 to 50 percent of patients Chest pain : same side of the chest as the primary tumor. Dull, aching, persistent pain  Dyspnea : 25 percent of cases obstructive pneumonitis Atelectasis Lymphangitic tumor spread Pneumothorax Pleural effusion Pericardial effusion 

Hoarseness : recurrent laryngeal nerve  Pleural involvement :typically exudates The yield of pleural fluid cytology after a single thoracentesis is about 60 percent, and the yield rises to 85 percent with three thoracenteses 

Superior vena cava syndrome :sensation of fullness in the head and dyspnea. Cough, pain, and dysphagia, Physical findings include dilated neck veins, a prominent venous pattern on the chest, facial edema, and a plethoric appearance, more common in patients with SCLC than NSCLC

Pancoast's syndrome :pain (usually in the shoulder, and less commonly in the forearm, scapula, and fingers), Horner's syndrome, bony destruction, and atrophy of hand muscles. 

Horner’s Syndrome miosis (constriction of the pupils), anhidrosis (lack of sweating),  ptosis (drooping of the eyelid) enophthalmos (sunken eyeball)

Extrathoracic metastases Liver  Bone  Adrenal  Brain 

Paraneoplastic phenomena Hypercalcemia:bony metastasis or secretion of a parathyroid hormone-related protein (PTHrP), calcitriol or other cytokines SIADH secretion :SCLC, Hyponatremia Neurologic: SCLC. Lambert-Eaton myasthenic syndrome (LEMS), cerebellar ataxia, sensory neuropathy, limbic encephalitis, encephalomyelitis, autonomic neuropathy, retinopathy, and opsomyoclonus  

Hematologic manifestations  — These include the following: Anemia — Anemia is frequent in patients with lung cancer and can contribute to fatigue and dyspnea Leukocytosis — granulocyte-colony stimulating factor Thrombocytosis Eosinophilia Hypercoagulable disorders

Hypertrophic osteoarthropathy :clubbing and periosteal proliferation

Diagnosis and staging HISTORY AND PHYSICAL EXAM LABORATORY TESTING: complete blood count, serum electrolytes, calcium, alkaline phosphatase, albumin, (ALT), (AST), total bilirubin, and creatinine 

DIAGNOSIS Chest radiographs may show the following: Pulmonary nodule, mass, or infiltrate Mediastinal widening Atelectasis Hilar enlargement Pleural effusion

Lung Cancer: Findings on Chest X-ray Nodule (< 3cm) vs. Mass (>= 3cm). Location: Peripheral (Adenocarcinoma) vs. Central (Squamous). Single or multiple (metastases). Endobronchial obstruction. Atelectasis of lobe or lung. Pneumonia.

IMAGING  All patients with suspected NSCLC should undergo contrast-enhanced computed tomography (CT) that extends through the lungs, liver, and adrenal glands. CT is ideal for tumor node metastasis (TNM) staging It can characterize the primary tumor and define its relationship to the chest wall and mediastinal structures It can identify mediastinal lymph nodes that are enlarged and suspicious for malignant involvement It can detect contralateral lung, chest wall, or upper abdominal lesions that are suspicious for metastasis

TISSUE SAMPLING  Primary tumor  — There are several options for sampling a primary tumor depending on the location: Conventional flexible bronchoscopy with forceps biopsy, blind transbronchial fine needle aspiration (TBNA), or both CT guided TTNA Pleural Tap Secondary Tumor

BRONCHOSCOPY

CT Guided TTNA

Common Paraneoplastic Syndromes: Syndrome Frequent Histology Hypercalcemia SIADH Cushing’s Syndrome Eaton-Lambert Squamous Cell Small Cell

Lymph nodes  Pleural effusion   Adrenal nodule

STAGING Based upon this initial evaluation, most patients require additional imaging. This may include whole body positron emission tomography (PET), integratedCT/PET, bone scanning, magnetic resonance imaging (MRI) of the chest wall or brain, and/or CT of the brain.

Staging for NSCLC : TNM classification Tumor size, L.Ns, Metastasis Staging of SCLC uses the Veterans Administration Lung Study Group designations of limited (confined to one hemithorax) or extensive (beyond one hemithorax)

Treatment  Surgery Chemotherapy Radiation therapy

Treatment  Surgical resection offers the best opportunity for long-term survival and cure in patients with resectable NSCLC: Lobectomy Resectability Operability

Non Small Cell Lung Cancer Contraindications to Surgical Resection Stage IIIB or IV. Extensive invasion into surrounding structures: Vena cava or atrium involvement. Recurrent laryngeal or phrenic nerve involvement. SVC obstruction, malignant effusion, pericardial tamponade. Contralateral lymph nodes.

Non Small Cell Lung Cancer Contraindications to Surgical Resection Medically unfit: Poor cardiac or pulmonary status. Predicted postoperative FEV1% < 40%. Predicted postoperative DLCO% < 40%. Exercise studies for marginal candidates.

1. PREOPERATIVE PULMONARY FUNCTION : >Spirometry : preop FEV 1 (<60 percent predicted) >Diffusing capacity

Lung Function to determine Operability Guidelines from the American College of Chest Physicians and the British Thoracic Society suggest that patients with a preoperative FEV 1 in excess of 2 L (or >80 percent predicted) generally tolerate pneumonectomy, whereas those with a preoperative FEV 1 greater than 1.5 L tolerate lobectomy

2. PREDICTED POSTOPERATIVE PULMONARY FUNCTION :  a combination of spirometry and quantitative perfusion lung scanning   Guidelines from the American College of Chest Physicians consider a patient to be at increased risk for lung resection with predicted postoperative values for either FEV 1 or DLCO <40 percent predicted 

3. MEASUREMENT OF GAS EXCHANGE Arterial PO2 Arterial PCO2

4. EXERCISE TESTING

REGIMENS Carboplatin plus docetaxel Carboplatin plus pemetrexed Cetuximab, vinorelbine, and cisplatin   Cisplatin plus pemetrexed   Gemcitabine plus carboplatin   Gemcitabine plus cisplatin (GC)   Paclitaxel carboplatin   Paclitaxel, carboplatin, and bevacizumab   Vinorelbine plus cisplatin  

RADIOTHERAPY SYMPTOM PALLIATION :Short courses of radiation therapy are useful for patients who require symptom palliation. This may include symptoms arising from progressive intrathoracic disease or disease at other sites (eg, bone, brain).

PALLIATIVE CARE Shortness of breath Pain Psychological Impairment

Prognosis of NSCLC Stage of disease Clinical parameters :Performance status , Ethnicity  Histopathology Molecular characterization :(EGFR), KRas PET and PET-CT: SUV number Recurrence after complete resection 

In Europe, the 5-year overall survival rate is 11% In Europe, the 5-year overall survival rate is 11%.  The highest recorded 5-year patient survival rates are observed in the United States. US data indicate that the 5-year relative survival rate for lung cancer was 17.4%, 

Estimated 5-year survival rates for specific stages of disease are as follows: Stage IA - 75% Stage IB - 55% Stage IIA - 50% Stage IIB - 40% Stage IIIA - 10-35% Stage IIIB - Less than 5% Stage IV - Less than 5%

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