Lung cancer

Prof. G.S. Moroz, MD Department of Oncology &

Radiology,Ternopil State Medical University

Epidemiology

Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality.

In 2008, there were 1.61 million new cases, and 1.38 million deaths due to lung cancer

Epidemiology The highest rates are in Europe and

North America. In the USA, the lifetime risk of

developing lung cancer is 8% in men and 6% in women.

Lung cancer incidence is currently less common in developing countries

Epidemiology Eastern Europe has the highest lung

cancer mortality among men, while northern Europe and the U.S. have the highest mortality among women.

In the United States, black men and women have a higher incidence.

Ukraine (2009) There were 17372 (crude rate = 37.80:

male/female = 14232/3140; crude rate = 67.18/12.67) new cases,

and 13645 (crude rate = 29.69: male/female= 11425/2220; crude rate= 53.93/8.96) deaths due to lung cancer

Etiology. There is a genetic predisposition to lung

cancer. In relatives of people with lung cancer, the risk is increased 2 times

Cancer develops following genetic damage to DNA, programmed cell death (apoptosis) or DNA repair.

As more damage accumulates, the risk of cancer increases

Smoking

is the main contributor to lung cancer The predominant cause of both small-cell lung

cancer and non–small-cell lung cancer is tobacco smoking. However, small-cell lung cancer is more strongly linked to smoking than non–small-cell lung cancer.

Cigarette smoke contains over 60 known carcinogens including radioisotopes from the radon decay, nitrosamine, and benzopyrene.

The incidence of lung cancer is highly correlated with smoking

Smoking 91% of lung cancer deaths in men

during the year 2000 were attributed to smoking (71% for women).

In the United States, smoking accounts for 80–90% of lung cancer cases.

The risk for lung cancer is 10 to 20 times higher in smokers than it is in nonsmokers.

Smoking

Passive smoke doubles the risk for lung cancer.

Those living with a smoker have a 30% increase in their risk of lung cancer.

Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.

Smoking After cessation of smoking, the risk

steadily declines approaching that of nonsmokers after 15 years of

abstinence for patients who smoked for less than 20 years.

Asbestos is causally linked to malignant

mesothelioma. Asbestos exposure also increases the

risk for lung cancer, especially in smokers (three times greater risk than smoking alone). Thus, the risk for lung cancer in smokers who are exposed to asbestos is increased 90-fold.

Ionizing radiation is a proven human carcinogen The evidence for this comes from studies of atomic bomb survivors in Japan,

people exposed during the Chernobyl nuclear accident, people treated with high doses of radiation for cancer, and people exposed to high levels of radiation at work, such as uranium miners.

Radon Radon is the second commonest cause

of lung cancer in the USA, after smoking.

The risk increases 8–16% for every 100 Bq/m3 increase in the radon concentration

Other substances associated with lung cancer include: arsenic, nickel, chromium compounds, chloromethyl ether, and air pollutants

Air pollution

Outdoor air pollution has a small effect on increasing the risk of lung cancer (1–2%).

Other lung diseases

Lung scars and chronic obstructive pulmonary disease are associated with an increased risk for lung cancer

Pathology and natural history Two main types of lung cancer exist:

non–small-cell lung cancer (NSCLC)  and small-cell lung cancer (SCLC, also called oat cell cancer).

Small-cell lung cancer accounts for approximately 20%-25% of all cases of lung cancer.

Clinico-anatomical classification Central form

Endobronchial Peribronchial nodulated Peribronchial branched

Clinico-anatomical classification Peripheral form

Rounded shadow Pneumonia-like Pancoast’s tumor

Clinico-anatomical classification Atypical form

Mediastinal Miliary carcinomatosis Cerebral Hepatic Osseous

Location.

More often central or hilar (95%) than peripheral (5%)

Non-small cell lung cancer

There are three main sub-types: adenocarcinoma, squamous cell lung carcinoma, and large cell lung carcinoma.

Nearly 40% of lung cancers are adenocarcinoma.

Squamous cell carcinoma accounts for about 30% of lung cancers.

About 9% of lung cancers are large cell carcinoma.

Small cell lung cancer

Small-cell lung cancer differs from non–small-cell lung cancer in the following ways: 

Small-cell lung cancer grows rapidly. Small-cell lung cancer spreads quickly.

Small cell lung cancer

Small-cell lung cancer responds well to chemotherapy and radiation therapy

Small-cell lung cancer is associated with paraneoplastic syndromes (a collection of symptoms that result from substances produced by the tumor).

Uncommon tumors of the lung Bronchial carcinoids Cystic adenoid carcinomas

("cylindroma") Carcinosarcomas Mesotheliomas

Signs and symptoms

One fourth of all people with lung cncer have no symptoms when the cancer is diagnosed

Symptoms and signs that may suggest lung cancer include:

Cough weight loss dyspnea (shortness of breath)

Signs and symptoms

Chest pain hemoptysis (coughing up blood) Bone pain Clubbing of the fingernails fever fatigue Superior vena cava obstruction Dysphagia (difficulty swallowing) Wheezing

Symptoms of metastatic cancer About 30-40% of people with lung

cancer have some symptoms or signs of metastatic disease:

Metastatic lung cancer in the liver may cause yellowing of the skin and eyes (jaundice)

Symptoms of metastatic cancer Lung cancer that has metastasized to

the bone causes bone pain. Lung cancer that spreads to the brain

can cause difficulties with vision, weakness on one side of the body, and/or seizures.

Paraneoplastic syndromes include the syndrome of inappropriate

antidiuretic hormone (SIADH), hyper-coagulable state ectopic adrenocorticotropic hormone

(ACTH) syndrome Eaton-Lambert (myasthenic) syndrome

Paraneoplastic syndromes hypertrophic osteoarthropathy, hypercalcemia and gynecomastia (large cell).

Symptoms of SC L C Persons with small-cell lung cancer typically have

had symptoms for a relatively short time (eight to 12 weeks) before they visit their doctor.  

  Symptoms due to local growth of the tumor include the following: Cough hemoptysis dyspnea

Symptoms of SC L C Symptoms due to spread of the cancer to

nearby areas include the following:  Hoarse voice, dyspnea,

Dysphagia, Swelling of the face and hands

Symptoms of SC L C Symptoms due to distant cancer spread

depend on the site of spread and include the following: Spread to the brain can cause headache,

blurring of vision, nausea, vomiting, weakness of any limb, mental changes, and seizures.

Spread to the vertebral column can cause back pain.

Symptoms of SC L C Spread to the spinal cord can cause

paralysis and loss of bowel or bladder function.

Spread to the bone can cause bone pain.

Spread to the liver can cause pain in the right upper part of the abdomen

Symptoms of SC L C Symptoms due to paraneoplastic

syndromes include the following: Symptoms may or may not be characteristic

of a specific organ system. Nonspecific symptoms include: fatigue, loss of appetite, and weight gain or loss.

Symptoms of SC L C Severe muscle weakness. Trouble with balance or walking. Changes in mental status. Changes in skin color, texture, and

facial features.

Diagnosis

Initial exams and tests for suspected lung cancer may include the following:

Medical, surgical, work, and smoking history

Physical exam to check for general signs of health

Chest X-ray 

Diagnosis CT scan of the chest Thoracentesis Bronchoscopy Mediastinoscopy

Diagnosis Performing a chest radiograph is one of

the first investigative steps This may reveal an obvious mass,

widening of the mediastinum atelectasis (collapse), consolidation

(pneumonia), or pleural effusion

Diagnosis CT imaging is typically used to provide

more information about the type and extent of disease.

Bronchoscopy or CT-guided biopsy is often used to take

sample the tumor for histopathology

Chest X-ray film

Chest X-ray film and CT

Chest X-ray film

X-ray tomogram

CT scan showing a cancer tumor in the left lung

Diagnosis Once the patient has been diagnosed

with lung cancer, exams and tests are performed to find out whether the cancer has spread (metastasized) to other organs.

Tests used to detect the spread of cancer may include the following:

Diagnosis Blood tests: Complete blood count

(CBC) provides information about the type and count of different types of blood cells, serum electrolytes, kidney function, and liver function.

CT scan of the chest and abdomen

Diagnosis MRI of the brain Radionuclide bone scan. If the cancer has

spread to the bones, the radioactive material collects in the bones and is detected by a scanner.

PET scan: a small amount of radioactive material is injected into the bloodstream and measures the metabolism of the organs to see if the cancer has spread. 

Staging

Staging is important because lung cancer treatment is based on the stage of the cancer.

Lung cancer staging is an assessment of the degree of spread of the cancer from its original source.

It is one of the factors affecting the prognosis and potential treatment of lung cancer

Staging The initial evaluation of non-small cell lung

cancer staging uses the TNM classification. This classification based on the size of the

primary tumor, lymph node involvement,

and distant metastasis. After this, a group is assigned, ranging from

IA to IV.

Staging system Stage Grouping Ia T1 NO MO Ib T2 NO MO IIa T1 N1 MO IIb T2 N1 MO; T3 NO MO IIIa T3 N1 MO;T1,2,3N2 MO IIIb Any T N3 MO; T4, Any N, MO IV Any T Any N M1

Staging Small cell lung cancer has traditionally

been classified as limited stage (confined to one half of the chest)

or extensive stage (more widespread disease).

Staging For both NSCLC and SCLC, there are two

general types of staging evaluations: Clinical Staging: evaluated prior to definitive

surgery, and typically based on the results of physical examination, imaging studies, and laboratory findings.

Pathological Staging: usually evaluated either intra- or post-operatively, and based on the combined results of surgical and clinical findings

Obtaining pathologic proof of lung cancer

Before embarking on other studies, a diagnosis of lung cancer must be proved histologically.

Morphological diagnosis

Sputum cytology Flexible fiberoptic bronchoscopy Suspicious cutaneous nodules Lymph nodes Percutaneous and transbronchial needle

biopsy Bone marrow aspiration and biopsy

Evaluation of the solitary pulmonary nodule Risk that a solitary pulmonary nodule is

malignant: a. According to age: (1) Younger than 35 years of age - less

than 2% (2) 35 to 45 years of age = 15% (3) Older than 45 years of age - 30% to

50%

According to tumor volume doubling time (DT)

DT of 30 days or less: less than 1% DT of 30 to 400 days: 30% to 50% DT of greater than 400 days: less than

1%

Treatment

Treatment for lung cancer depends on the cancer's specific cell type, how far it has spread and the patient's performance status.

Common treatments include: palliative care, surgery, chemotherapy, and radiation therapy

Signs of unresectable NSCLC

a. Distant metastases b. Persistent pleural effusion, with

malignant cells c.Superior vena cava obstruction

Signs of unresectable NSCLC d. Involvement of the following structures: (1) Supraclavicular or neck lymph nodes

(proved histologically) (2) Contralateral mediastinal lymph nodes

(proved histologically) (3) Recurrent laryngeal nerve (4) Tracheal wall (5) Main-stem bronchus less than 2 cm from

the carina (resectable by sleeve resection technique)

Management of operable disease (NSCLC)

a. Incomplete resections: wedge resection or segmentectomy

b. Lobectomy c. Bilobectomy d. sleeve resection of the lesions e. pneumonectomyf. Video-assisted thoracoscopic surgery

(VATS)

Management of operable disease (NSCLC)

However, wedge resection may be performed only in patients who are unfit for a full lobectomy, because wedge resection has a higher risk of recurrent disease than lobectomy.

Radioactive iodine brachytherapy at the margins of wedge excision may reduce the risk of recurrence.

Treatment (SCLC) In small-cell lung cancer (SCLC),

chemotherapy and/or radiation therapy is typically used.

However the role of surgery in SCLC is being reconsidered.

Surgery might improve outcomes when added to chemotherapy and radiation in.

Recently are used other methods of treatment of lung cancer

Laser therapy Electrosurgery Radiosurgery

Radiotherapy

is often given together with chemotherapy, and may be used with curative intent in patients with non-small-cell lung cancer who are not eligible for surgery.

This form of high intensity radiotherapy is called radical radiotherapy

Radiotherapy

For small-cell lung cancer cases that are potentially curable, chest radiation is often recommended in addition to chemotherapy.

Radiotherapy Post-operative thoracic radiotherapy

generally should not be used after curative intent surgery for non-small-cell lung cancer.

Some patients with mediastinal lymph node involvement (N2) might benefit from post-operative radiotherapy.

Radiotherapy

RT has been employed as the

preliminary treatment for Pancoast's tumors (T3 NO MO, stage IIb) before surgical resection of the primary tumor and involved chest wall.

Radiotherapy Prophylactic cranial irradiation (PCI) is a

type of radiotherapy to the brain, used to reduce the risk of metastasis.

PCI is most useful in small-cell lung cancer.

PCI increases three-year survival from 15% to 20%.

Radiotherapy For both non-small cell lung cancer and

small cell lung cancer patients, smaller doses of radiation to the chest may be used for symptom control (palliative radiotherapy).

Chemotherapy (SCLC)

are most commonly used: cisplatin and etoposide Combinations with carboplatin, gemcitabine,

paclitaxel, vinorelbine,topotecan, and irinotecan are also used

Chemotherapy (NSCLC) Typically, two drugs are used, of which

one is often platinum-based (either cisplatin or carboplatin).

Other commonly used drugs are: gemcitabine, paclitaxel and docetaxel.

Pancoast's tumor

RT has been employed as the preliminary treatment for Pancoast's tumors (T3 NO MO, stage IIb) before surgical resection of the primary tumor and involved chest wall.

Novel Therapeutic Approaches Signal transduction inhibitors/cell cycle

regulators Angiogenesis inhibitors Gene therapy Biologic and immunotherapy (vaccines,

oncolytic viruses) Hypoxic cytotoxins (target: hypoxic cancer

cells resistant to chemotherapy)

Prognosis

Prognosis is generally poor. Of all patients with lung cancer, 15%

survive for five years after diagnosis. 30–40% of cases of non-small cell lung

cancer (NSCLC) are stage IV, and 60% of small cell lung cancer

(SCLC) are stage IV

Prognosis For NSCLC, following complete surgical

resection of stage IA disease, five-year survival is 67%.

For SCLC, the overall five-year survival for patients is about 5%.

Stage-specific median survival time Stage Ia – more than 60 months Stage Ib – about 36 months Stage IIa – about 24 months Stage IIb – about 20 months Stage IIIa – about 15 months Stage IIIb – about 12 months Stage IV – about 8 months

Prevention

Eliminating tobacco smoking is a primary goal in the prevention of lung cancer.

The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer.

Linus Pauling, Ph.D. (1901-1994)

was the only person ever to win two unshared Nobel prizes.

He received these awards for chemistry in 1954 and for peace in 1962.

Pauling is largely responsible for the widespread misbelief that high doses of vitamin C

are effective against colds and other illnesses (cancer). He took 18,000 mg of vitamin C daily but died from

cancer.

Screening refers to the use of medical tests to

detect disease in asymptomatic people. Possible screening tests for lung

cancer include: sputum cytology, chest radiograph, and CT.

Follow-up 

Patients who are receiving chemotherapy require close monitoring for side effects and response to therapy.

A blood workup, including complete blood count (CBC), is needed prior to each cycle of chemotherapy. 

Follow-up Kidney function is monitored, especially

if the patient is taking platinum-based chemotherapy as it can damage the kidneys.

The patient will undergo a CT scan to assess their response to treatment.

Other tests are performed to monitor liver function and electrolytes.

The mediastinumThe mediastinum

Anatomy. The mediastinum is bounded by the sternum anteriorly, the thoracic vertebral bodies posteriorly, the diaphragm inferiorly, and the first thoracic vertebrae superiorly. Its lateral boundaries are the parietal and pleural surfaces of the lungs.

` The mediastinum` The mediastinum

Traditionally, the mediastinum is artificially subdivided into anterior, middle, and posterior segments by the heart and great vessels.

The mediastinum

MEDIASTINUM TUMORS

Incidence.

The annual incidence of mediastinal tumors is 2 per 1 million populations. Seventy-five percent of mediastinal tumors are benign

Anterior (front) mediastinum

Germ cell - The majority of germ cell neoplasms (60 to 70%) are benign and are found in both males and females.

Lymphoma – Malignant tumors that include both Hodgkin’s disease and non Hodgkin’s lymphoma.

Anterior (front) mediastinum

Thymoma and thymic cyst - The most common cause of a thymic mass, the majority of thymomas are benign lesions that are contained within a fibrous capsule. However, about 30% of these may be more aggressive and become invasive through the fibrous capsule.

Thyroid mass mediastinal – Usually a benign growth, such as a goiter, these can occasionally be cancerous.

Middle mediastinum

Bronchogenic cyst – A benign growth with respiratory origins.

Lymphadenopathy mediastinal – An enlargement of the lymph nodes.

Pericardial cyst – A benign growth that results from an "out-pouching" of the pericardium (the heart’s lining).

Middle mediastinum

Thyroid mass mediastinal – Usually a benign growth, such as a goiter. These types of tumors can occasionally be cancerous.

Tracheal tumors – These include tracheal neoplasms and non-euplastic masses, such as tracheobronchopathia osteochondroplastica (benign tumors).

Vascular abnormalities including aortic aneurysm and aortic dissection.

Posterior (back) mediastinum

Extramedullary haematopoiesis – A rare cause of masses that form from bone marrow expansion and are associated with severe anemia.

Lymphadenopathy mediastinal – An enlargement of the lymph nodes.

Neuroenteric cyst mediastinal – A rare growth, which involves both neural and gastrointestinal elements.

Posterior (back) mediastinum

Neurogenic neoplasm mediastinal – The most common cause of posterior mediastinal tumors, these are classified as nerve sheath neoplasms, ganglion cell neoplasms, and paraganglionic cell neoplasms. Approximately 70% of neurogenic neoplasms are benign.

MEDIASTINUM TUMORS Oesophageal abnormalities including

achalasia oesophageal, oesophageal neoplasm and hiatal hernia.

Paravertebral abnormalities including infectious, malignant and traumatic abnormalities of the thoracic spine.

MEDIASTINUM TUMORS Thyroid mass mediastinal – Usually a

benign growth, such as a goiter, which can occasionally be cancerous.

Vascular abnormalities – Includes aortic aneurysms.

Age and sex.

Most of the tumors show no sexual predilection. Mediastinal teratomas usually arise after the age of 30 years. Benign thymomas may occur in any age group. Thymic carcinomas are more common in elderly men. Tumors of nerve tissue origin may occur at any age but are more common in children.

Age and sex.Age and sex.Age and sex.

Symptoms and signs

Presenting symptoms depend on the tumor location, type, and rate of growth

Anterior mediastinal tumors

can present with retrosternal pain, dyspnea, upper airway obstruction, and development of collateral venous circulation over the chest

Posterior mediastinal tumors

can cause tracheal compression (cough and dyspnea), phrenic nerve compression (hiccoughs or diaphragm paralysis), involvement of left recurrent laryngeal nerve (hoarseness), esophageal compression (dyspbagia), vena cava obstruction

Tumors of the anterior and middle mediastinum

Thymomas represent 20% of all mediastinal tumors

Thymomas are benign in 70% of cases and are locally invasive in 30%.

A PA chest x-ray revealing soft tissue fullness in the left paratracheal region of the superior mediastinum.

A select enhanced axial CT image at the level of the antero-superior mediastinal mass, which is hyperdense and mildly inhomogeneous

displacing the trachea to the right

Paraneoplastic syndromes

Myasthenia gravis

Pure red-cell aplasia

Acquired hypogammaglobulinemia

Rare paraneoplastic syndromes associated with

thymoma(a) Ectopic Cushing's syndrome

(b) Polymyositis, dermatomyositis, granulomatous myocarditis

(c) Systemic lupus erythematosus(d) Hypertrophic osteoarthropathy

Therapy

Surgical extirpation

Radiation therapy (RT), 3000 to 5000 cGy

Combination chemotherapy

regimens for locally advanced or metastatic disease usually involve cisplatin, doxorubicin, and cyclophosphamide

Thymic carcinomas

Thymic carcinoids

Germ cell tumors

Benign teratoma

Seminoma

Mediastinal nonseminomatous germ cell tumors

Other anterior mediastinal masse

a. Goiter and thyroid cysts (10% of mediastinal masses)

b. Lymphomasc. Parathyroid adenoma (10% are ectopic)

Rare causes of anterior mediastinal masses

(1) Thymic cysts(2) Thymolipoma

(3) Lymphangioma (cystic hygroma)

(4) Soft tissue sarcomas and their benign counterparts (5) Plasmacytoma

Middle mediastinal massesa. Lymphomas

b. Goiterc. Aortic aneurysm (10% of mediastinal

masses in surgical series)d. Congenital foregut cysts (20% of mediastinal masses). About 50% of

foregut cysts are bronchogenic, 10% are enterogenous (including

esophageal duplication), and 5% are neuroenteric.

e. Pericardial cysts

Tumors of the posterior mediastinum

Neurogenic tumors

Mesenchymal tumors

Other posterior mediastinal masses

a. Lymphomasb. Goiter

c. Lateral thoracic meningocele