1

Lung Cancer

Feras I. Hawari, M.D

Feras I. Hawari, MD, FCCP

Director, Cancer Control Office

Chief, Section of Pulmonary and Critical Care

King Hussein Cancer Center

Director, Global Bridges, EMR

2

• Lung Cancer is on the rise• It is the second cancer in males in

Jordan after colon cancer• More than 300 cases /year

3

• Malignancies that originate in the airways or pulmonary parenchyma.

• Classified as:– Small cell lung cancer (SCLC) –Non-small cell lung cancer (NSCLC).

4

Risk Factors• Smoking:– The primary risk factor for the development of lung

cancer.– 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.

– Extent of smoking and exposure to other carcinogenic factors, such as asbestos increase the risk

5

Risk Factors• Radiation therapy :

– Hodgkin lymphoma– Breast cancer

• Environmental toxins :– exposure to second-hand smoke– Asbestos, radon, metals (arsenic, chromium, and nickel),

ionizing radiation, and polycyclic aromatic hydrocarbons

• Pulmonary fibrosis : the risk is increased sevenfold patients with pulmonary fibrosis and is independent of smoking

• HIV infection

6

Risk Factors• Genetic factors: familial risk • Dietary factors : antioxidants,

cruciferous vegetables, phytoestrogens may reduce the risk of lung cancer

• Alpha-Tocopherol: Beta-Carotene Cancer Prevention Study actually showed an increase in lung cancer among smokers with dietary supplementation of beta-carotene

7

Screening• Low dose spiral CT scan showed

reduced mortality by 20% in specific setting but is not yet recommended as a national screening strategy

8

Pathological Classification

• Adenocarcinoma (including bronchioloalveolar carcinoma) : 38%

• Squamous cell carcinoma: 20%• Large cell carcinoma: 5%• Small cell carcinoma: 13%• Other non-small cell carcinomas: 18%• Others: 6%

9

Clinical Presentation• The majority present with advanced

disease• Cough: 50-75%–Watch for the smokers cough–Bronchorrhea: cough productive of large

volumes of thin mucoid secretions may be a feature of bronchoalveolar cell carcinoma and usually indicates advanced disease

10

Clinical Presentation• Hemoptysis: 25-50%• Chest pain: 20%• Dyspnea:25%• Hoarseness of voice: tumor involving

the recurrent laryngeal nerve along its course under the arch of the aorta and back to the larynx

11

• Pleural effusion:10-15%• Superior vena cave syndrome: more

common in patients with SCLC than NSCLC– sensation of fullness in the head and dyspnea. – Physical findings:• Dilated neck veins• Prominent venous pattern on the chest• Facial edema• Plethoric appearance

12

13

Pancoast Syndrome• Pancoast syndrome: most commonly caused by

NSCLC (typically squamous cell), rarely by SCLC  • Lung cancers arising in the superior sulcus cause a

characteristic Pancoast syndrome:– Pain (usually in the shoulder, and less commonly in the

forearm, scapula, and fingers)– Horner's syndrome (oculosympathetic paresis ): miosis,

ptosis, and anhidrosis. Produced by a lesion anywhere along the sympathetic pathway that supplies the head, eye, and neck

– Bony destruction– Atrophy of hand muscles

14

15

Metastasis• Bone• Brain• Liver• Adrenal

16

Paraneoplastic Syndromes

• Hypercalcemia: – Bony metastasis – less commonly tumor secretion of a parathyroid

hormone-related protein (PTHrP), calcitriol or other cytokines, including osteoclast activating factors

• Squamous cell carcinoma was responsible in 51%

• Most patients with hypercalcemia have advanced disease (stage III or IV) and a median survival of a few months

17

Paraneoplastic Syndromes

• SIADH secretion– Frequently caused by SCLC 75% of all

malignancy related hyponatremia.–Hyponatremia (the presenting feature in

10% of SCLC patients)

• Treating the malignancy• Hyponatremia will resolve within

weeks of starting chemotherapy.

18

Paraneoplastic Syndromes

• neurologic syndromes:• Thought to be immune-mediated, and autoantibodies

have been identified in a number of instances– Lambert-Eaton myasthenic syndrome (LEMS)– Cerebellar ataxia– Sensory neuropathy– Limbic encephalitis– Encephalomyelitis– Autonomic neuropathy– Retinopathy– Opsomyoclonus

19

LEMS• May be seen in 3 percent of patients

with SCLC• The neurologic symptoms of LEMS

precede the diagnosis of SCLC in more than 80 percent of cases, often by months to years

20

LEMS• Disorder of neuromuscular junction

transmission disorder of reduced ACh release from the presynaptic nerve terminals, despite normal ACh vesicle number, presynaptic concentration, and postsynaptic ACh receptors

21

LEMS• Antibodies directed against the

voltage-gated calcium channel (VGCC) interfere with the normal calcium flux required for the release of acetylcholine.

22

LEMS• Clinically:– Slowly progressive proximal muscle weakness,

particularly involving the legs– Deep tendon reflexes are typically depressed or

absent– Dry mouth is the most common autonomic symptom– Ocular symptoms, especially ptosis and diplopia,

may occur with LEMS but are rare– Most patients do not have significant respiratory

muscle weakness, but respiratory failure may occur late in the course

23

LEMS• Recovery of lost deep tendon reflexes or improvement in

muscle strength with vigorous, brief muscle activation is a unique aspect of LEMS

• The diagnosis of LEMS:– Clinical grounds– Confirmed by the presence of antibodies directed against

VGCCs and by electrodiagnostic studies. A high titer P/Q-type VGCC antibody is strongly suggestive of LEMS in the appropriate clinical setting.

– P/Q-type VGCC antibodies are present in a variety of clinical situations where LEMS is not present.

– Confirmed by a reproducible postexercise increase in compound muscle action potential amplitude of at least 100 percent compared with pre-exercise baseline value.

24

Hematological• Anemia: 40%• Leukocytosis: 15%, due to

overproduction of GCSF, associated with poor prognosis and hypercalcemia [

• Thrombocytosis: shortened survival• Eosinophilia : in tissue or blood is rare,

but has been reported in patients with large cell carcinoma

25

Hypercoagulable Disorders

• Trousseau's syndrome (migratory superficial thrombophlebitis)

• DVT/Embolism• DIC• Thrombotic microangiopathy• Nonthrombotic microangiopathy

26

Hypertrophic osteoarthropathy • HPO: presence of clubbing and

periosteal proliferation of the tubular bones

• symmetrical, painful arthropathy: ankles, knees, wrists, and elbows. The metacarpal, metatarsal, and phalangeal bones may also be involved.

27

28

29

• Symptoms of HPO resolve after tumor resection

• For patients who are not operable, the usual treatment is with NSAIDS or bisphosphonate

30

• Dermatomyositis and polymyositis • Cushing's syndrome: – Ectopic production of ACTH–Common in patients with SCLC,

carcinoid tumors of the lung–Have a worse prognosis

31

Initial Evaluation• Clinical extent and stage of disease• Optimal target site and modality for the first

tissue biopsy • Specific histological subtype• Presence of comorbidities, secondary

complications, and paraneoplastic syndromes that influence treatment options and outcome

• Patient values and preferences that influence diagnostic and therapeutic choices

32

33

• Complete blood count• Electrolytes• Calcium• Alkaline phosphatase• Alanine aminotransferase (ALT) and

aspartate aminotransferase (AST) • Total bilirubin• Creatinine

34

• Every patient with suspected NSCLC should undergo CT scan of the chest and upper abdomen (usually contrast-enhanced) to evaluate the extent of the primary tumor and potential spread to the mediastinum, liver, and adrenal glands. Radiographic staging does not obviate the need for tissue biopsy

35

• Reserve PET or integrated PET/CT for use in operable patients with CT stage IB to IIIA disease, ie, those with potentially resectable tumors at high risk for minimal or occult N2 lymph node involvement.

• Consider PET for select patients with clinical stage IA (T1N0M0) disease prior to curative surgery.

36

• Routine imaging to screen for distant metastases is not required for every case of suspected NSCLC

• Imaging for metastatic disease should be symptom-focused or CT-directed

• Gadolinium-enhanced MRI of the brain is used to evaluate symptomatic patients for brain metastases and to assess asymptomatic patients with clinical stage III or IV NSCLC

37

Management of stage I and stage II non-small cell lung cancer

• For patients with adequate PFT and without serious medical comorbidity: surgical resection for stage I or II NSCLC – Lobectomy (VATS vs. open) – Pneumonectomy

• Stereotactic body radiation therapy (SBRT) is an alternative for those not accepting surgery

38

• For patients with small primary tumors (less than 5 cm) and impaired pulmonary function or medical comorbidity that precludes surgical resection and for those who refuse surgery:– Stereotactic body radiation therapy

(SBRT)

Management of stage I and stage II non-small cell lung cancer

39

Adjuvent Therapy• No need for stage 1A• Stage IB NSCLC: who are willing and

able to tolerate adjuvant chemotherapy: adjuvant chemotherapy with a platinum-based particularly for primary tumors measuring 4 cm or larger in greatest. Observation is an option

40

Adjuvent Therapy• No need for adjuvant RT following

complete resection of stage I and II NSCLC with negative resection margins. Use for those with positive margins.

41

Treatment of advanced non-small cell lung cancer

• Four to six cycles of cytotoxic chemotherapy with a platinum-based doublet. For patients with nonsquamous NSCLC

• For patients whose tumor contains a driver mutation, use of a specific inhibitor is the preferred initial approach eg. Erlotinib etc… or Afatinib for patients with an activating mutation of EGFR, Crizotininb for those with the ALK fusion oncogene

42

Management of stage III non-small cell lung cancer

• For patients with pathologically negative mediastinal lymph nodes including pathologic evaluation (T3N1), we recommend surgery if a complete resection is technically feasible

• Adjuvant chemotherapy following resection . If a complete resection is not technically feasible, concurrent chemoradiotherapy is indicated

43

Management of stage III non-small cell lung cancer

• For patients with pathologic involvement of mediastinal lymph nodes (N2 or N3) and whose overall medical condition and performance status is acceptable: initial treatment with concurrent chemoradiotherapy followed by surgery for carefully selected:– Healthy patients with non-bulky mediastinal

lymph node involvement whose tumor can be resected with a lobectomy

44

Obtaining Tissue Diagnosis

• Bronchoscopy• EBUS/EUS• CT-guided biopsy• Medistinoscopy• Electro magnetic navigation system

45

46

47

48

49

Preoperative Evaluation

• PFT: FEV1 >80% (pneumonectomy), 65% (lobectomy)

• CPET: if FEV1 or DLCO <80%• Split perfusion scan:

50

51

Small Cell Lung CA• Usually central• Short doubling time• 60-70% present with metastasis• Highly responsive to chemo and radio• Usually relapses within two years despite

treatment• Only 10 to 15 percent of patients with limited

stage SCLC and 1 to 2 percent of patients with extensive stage SCLC survive beyond five years

52

Staging• Limited disease – Tumor confined to the

ipsilateral hemithorax and regional nodes, including ipsilateral supraclavicular involvement, able to be included in a single tolerable radiotherapy port (corresponding in part to TNM stages I through IIIB).

• Extensive disease – Tumor beyond the boundaries of limited disease including distant metastases, malignant pericardial, or pleural effusions, and contralateral supraclavicular and contralateral hilar involvement

53

Treatment• For patients who have been diagnosed

with SCLC in a solitary pulmonary nodule, who have no evidence of hilar or mediastinal nodal involvement or distant metastases after a thorough staging evaluation, and who have no other contraindication to surgery: surgical resection followed by chemo

54

Treatment• Patients with limited stage disease:

combined chemo/radio therapy• For patients with extensive stage SCLC:

chemotherapy alone• Prophylactic RT decreases the incidence

of brain metastases and prolongs survival in patients with both limited and those with extensive stage SCLC who respond to their initial treatment

55

56

57

Adapted from Nutt et al, Lancet 2007;369:1047-1053

Ranking of Substance Dependence(Scale 0 – 3)

SubstanceMean

Dependence

Pleasure

Psychological

Dependence

Physical Dependen

ce

Heroin 3.00 3.0 3.0 3.0

Cocaine 2.39 3.0 2.8 1.3

Tobacco 2.21 2.3 2.6 1.8

Alcohol 1.93 2.3 1.9 1.6

Amphetamine

1.67 2.0 1.9 1.1

Cannabis 1.51 1.9 1.7 0.8

58

THANK YOU

2016