1. Lung Cancer 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 : Environmental toxins :
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

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

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.

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

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

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

49. Preoperative Evaluation
PFT: FEV1 >80% (pneumonectomy), 65% (lobectomy)
CPET: if FEV1 or DLCO <80%
Split perfusion scan:

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

57. Ranking of Substance Dependence
(Scale 0 – 3)
Substance
Mean
Dependence
Pleasure
Psychological
Physical
Heroin
3.00
3.0
Cocaine
2.39
2.8
1.3
Tobacco
2.21
2.3
2.6
1.8
Alcohol
1.93
1.9
1.6
Amphetamine
1.67
2.0
1.1
Cannabis
1.51
1.7
0.8
Adapted from Nutt et al, Lancet 2007;369:

58. THANK YOU
2016