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Lung Cancer Information

Lung cancer is a cancer of the lungs characterized by the presence of malignant tumours. Most commonly it is bronchogenic carcinoma (about 90%). Lung cancer is one of the most lethal of cancers worldwide, causing up to 3 million deaths annually. Only one in ten patients diagnosed with this disease will survive the next five years. Although lung cancer was previously an illness that affected predominately men, the lung cancer rate for women has been increasing in the last few decades, which has been attributed to the rising ratio of female to male smokers.

Current research indicates that the factor with the greatest impact on risk of lung cancer is long-term exposure to inhaled carcinogens. The most common means of such exposure is tobacco smoke.

Treatment and prognosis depend upon the histological type of cancer and the stage (degree of spread). Possible treatment modalities include surgery, chemotherapy, and/or radiotherapy.

Performing a chest X-ray is the first step if a patient reports symptoms that may be suggestive of lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (infection) and pleural effusion. If there are no X-ray findings but the suspicion is high (e.g. a heavy smoker with blood-stained sputum), bronchoscopy and/or a CT scan may provide the necessary information. In any case, bronchoscopy or CT-guided biopsy is often necessary to identify the tumor type.

If investigations have confirmed lung cancer, scan results and often positron emission tomography (PET) are used to determine whether the disease is localised and amenable to surgery or whether it has spread to the point it cannot be cured surgically. PET is not useful as screening, as not all malignancies are positive on PET scan (such as bronchoalveolar carcinoma), and lung infections may be positive on PET Scan.

Blood tests and spirometry (lung function testing) are also necessary to assess whether the patient is well enough to be operated on. If spirometry reveals a very poor respiratory reserve, as may occur in chronic smokers, surgery may be contraindicated.

There are two main types of lung cancer categorized by the size and appearance of the malignant cells seen by a histopathologist under a microscope: non-small cell (80%) and small-cell (roughly 20%) lung cancer. This classification although based on simple pathomorphological criteria has very important implications for clinical management and prognosis of the disease.

The non-small cell lung cancers (NSCLC) are grouped together because their prognosis and management is roughly identical. The subtypes are:

Squamous cell carcinoma, accounting for 20% to 25% of NSCLC, also starts in the larger breathing tubes but grows slower meaning that the size of these tumours varies on diagnosis.

Adenocarcinoma is the most common subtype of NSCLC, accounting for 50% to 60% of NSCLC. It is a form which starts near the gas-exchanging surface of the lung. Most cases of the adenocarcinoma are associated with smoking. However, among non-smokers and in particular female non-smokers, adenocarcinoma is the most common form of lung cancer. A subtype of adenocarcinoma, the bronchioalveolar carcinoma, is more common in female non-smokers and may have different responses to treatment.

Large cell carcinoma is a fast-growing form that grows near the surface of the lung. It is primarily a diagnosis of exclusion, and when more investigation is done, it is usually reclassified to squamous cell carcinoma or adenocarcinoma.

Small cell carcinoma (SCLC, also called "oat cell carcinoma") is the less common form of lung cancer. It tends to start in the larger breathing tubes and grows rapidly becoming quite large. The oncogene most commonly involved is L-myc. The "oat" cell contains dense neurosecretory granules which give this an endocrine/paraneoplastic syndrome association. It is more sensitive to chemotherapy, but carries a worse prognosis and is often metastatic at presentation. This type of lung cancer is strongly associated with smoking.

Other types of lung cancer include carcinoid (the main representatives in this group), adenoid cystic carcinoma, cylindroma and mucoepidermoid carcinoma.

The lung is a common place for metastasis from tumors in other parts of the body. These cancers, however, are identified by the site of origin, i.e., a breast cancer metastasis to the lung is still known as breast cancer. The adrenal glands, liver, brain, and bone are the most common sites of metastasis from primary lung cancer itself.

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 surgery, chemotherapy, and radiation therapy.

Surgery is only an option in NSCLC and if the disease is limited to one lung and has not spread beyond its confines. This is assessed with medical imaging (computed tomography, positron emission tomography). Furthermore, as stated, a sufficient respiratory reserve needs to be present to allow for the removal of large amounts of lung tissue. Procedures performed include lobectomy (removal of one lobe), bilobectomy (two lobes) or pneumonectomy (removal of a whole lung).

The role of sublobar resection (extended wedge resection)continues to be debated for the primary management of NSCLC. Although overall survival appears to be equivalent to that of lobectomy resection, the local recurrence rate has been documented to be over three times more common (19% compared to 5%). Accordingly, sublobar resection has historically been used as a "compromise resection" approach for the management of small (less than 3 centimeters diameter)stage I peripheral NSCLC identified in patients with impaired cardiopulmonary reserve. Recent reports of the use of intraoperative radioactive iodine brachytherapy implants at the margins of sublobar resection suggest that local recurrence can be reduced to that of lobectomy when this is used as a surgical adjunct to sublobar resection.

The role of anatomic segmentectomy (a larger sublobar resection) with complete lymph node staging has also been found to have potential survival benefits similar to lobectomy. Such resections should be limited to peripheral small (less than 2 centimeter diameter)stage I NSCLC where a margin of resection equivalent to the diameter of the tumor can be achieved.

Five-year prognosis is often as good as 70% following complete resection of limited (lesions limited to the lung tissue without lymph node spread - stage 1) disease.

After surgery, adjuvant chemotherapy may be recommended if lymph nodes within the lung tissues resected (stage 2) or the mediastinum (lymph nodes in the peri-tracheal region -stage 3) are found to be positive for cancer spread. Survival may be improved by up to 15% above patients receiving only surgical resection in these circumstances. The role of adjuvant chemotherapy for patients with large stage 1 NSCLC (tumors greater than 3 centimeters diameters without lymph node involvement - stage 1b) remains controversial.

Only one randomized study (yet to be published), which was recently conducted by the Cancer and Leukemia -Group B (CALGB)-2004 demonstrated survival benefit with the addition of chemotherapy following surgical resection of stage 1B disease. An update of the data from the CALGB trial mentioned above presented at the 2006 ASCO (American College of Clinical Oncology) annual meeting revealed that the survival advantage previously reported by them in 2004 for stage 1B patients receiving adjuvant chemotherapy in their trial no longer demonstrated a significant survival advantage compared to patients managed with surgical resection alone.

Three other recent contemporary studies to the CALGB trial mentioned above examining the use of adjuvant chemotherapy for Stage IB non-small cell lung cancer have also not demonstrated a survival benefit for patients undergong chemotherapy after complete resection of this stage of non-small cell lung cancer (IALT-2003, NCI Canada 2004, ANITA 2005). Adjuvant chemotherpay following the complete resection of more advanced stages of non-small cell lung cancer (stages 2 and 3A) did appear to provide a survival advantage over surgical resection alone.

Small-cell lung cancer is treated primarily with chemotherapy, as surgery has no demonstrable influence on survival. Primary chemotherapy is also given in metastatic NSCLC.

The combination regimen depends on the tumour type:

NSCLC: cisplatin or carboplatin, in combination with gemcitabine, paclitaxel, docetaxel, etoposide or vinorelbine. In metastatic lung cancer, the addition of bevacizumab when added to carboplatin and paclitaxel was found to improve survival (though in this study, patients with squamous cell lung cancer were excluded because of problems with pulmonary hemorrhage in this group in the past).

SCLC: cisplatin or carboplatin, in combination etoposide or ifosfamide; combinations with gemcitabine, paclitaxel, vinorelbine, topotecan and irinotecan are being studied

In recent years, various molecular targeted therapies have been developed for the treatment of advanced lung cancer. Gefitinib (Iressa®) is one such drug, which targets the epidermal growth factor receptor (EGF-R) which is expressed in many cases of NSCLC. However despite an exciting start it was not shown to increase survival, although younger females without a smoking history appear to be deriving most benefit from gefitinib.

A newer drug called erlotinib (Tarceva®) has been shown to increase survival in lung cancer patients and has recently been approved by the FDA for second-line treatment of advanced non-small cell lung cancer.[2]

Treatment of non-small cell lung cancer is evolving and the next few years could present exciting developments and new targeted therapies for lung cancer.

Radiotherapy is often given together with chemotherapy, and may be used with curative intent in patients who are not eligible for surgery. A radiation dose of 40 or more Gy in many fractions is commonly used with curative intent in non-small cell lung cancer; typically in North America, the dose prescribed is 60 or 66 Gy in 30 to 33 fractions given once daily, 5 days a week, for 6 to 6 1/2 weeks. For small cell lung cancer cases that are potentially curable, in addition to chemotherapy, chest radiation is often recommended. For these small cell lung cancer cases, chest radiation doses of 40 Gy or more in many fractions are commonly given; typically in North America, the dose prescribed is 45 to 50 Gy and can be given in either once daily treatments for 5 weeks or twice daily treatments for 3 weeks.

For both non-small cell lung cancer and small cell lung cancer patients, radiation of disease in the chest to smaller doses (typically 20 Gy in 5 fractions) may be used for symptom control.

Radiofrequency ablation is increasing in popularity for this condition as it is nontoxic and causes very little pain. It seems especially effective when combined with chemotherapy as it catches the cells inside a tumor—the ones difficult to get with chemotherapy due to reduced blood supply to the inside of the tumor. It is done by inserting a small heat probe into the tumor to cook the tumor cells. The body then disposes of the cooked cells through its normal eliminative processes.

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