There are 1.35 million new lung cancer cases each year [1]
1.01 million of all new lung cancer cases in the world each year are Non-Small Cell Lung Cancer (NSCLC). [1,2] This section focuses on the main aspects of lung cancer, with a focus on NSCLC, including epidemiology, risk factors, the different types of lung cancer, staging of the disease and current therapies.
Types of lung cancer
Each type of lung cancer responds differently to various treatments, so the proper classification is necessary before beginning any therapy.
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Although lung cancer is the most preventable cancer, it is also the most common and causes more deaths worldwide than any other. [1,3]
While the incidence of lung cancer in some nations has started to decrease, the numbers worldwide are likely to be offset by rising rates in certain eastern European countries and future increases in developing nations. [4,5] A few statistics to put it in perspective:
- Only 1 in every 10 people diagnosed with lung cancer is still alive five years after diagnosis. [2]
- Lung cancer accounts for 12.4% of the total cases of cancer in the world. [1]
- There are 1.1 million deaths due to lung cancer per year, 17.2% of the deaths due to cancer worldwide. [5,6]
- Every 30 seconds someone in the world dies of lung cancer. [2]
Main risk factors of developing lung cancer include: [7]
- Cigarette smoking
- including secondhand smoke
- Occupational exposure to carcinogens
- tar and soot
- metals such as chromium and arsenic
- Exposure to radiation
- radon gas
- x-rays
- gamma rays
- Exposure to building materials
- silicates
- asbestos
- Outdoor air pollution
- traffic fumes, especially diesel exhaust
- Indoor air pollution
- produced by combustion for heating and cooking
75% of lung cancers are NSCLC
Non-Small Cell Lung Cancer (NSCLC) is the most common form of lung cancer and accounts for the most deaths of any cancer worldwide. [2] It is not one type of cancer, but an aggregate of different histologies that have been grouped together because approaches to diagnosis, staging, prognosis and treatment are similar. [9]
Staging and treatment options for NSCLC
In patients with lung cancer, clinical staging based on chest radiography, CT of the chest and upper abdomen and evaluation of the patient’s performance status is effective for treatment planning. [10]
Staging is done by assessing the amount and the size of tumors (T), the amount of nodal involvement (N) and the degree of metastasis (M). In general: [10]
- Hidden stage: cancer is too small to be seen, but cancer cells are detected in sputum
- Stage 0: cancer is only found in the original tumor
- Stage I: cancer is confined to one part of the lung
- Stage II: cancer has spread to nearby lymph nodes or tissues
- Stage III: cancer has spread more extensively within the chest and usually to the major lymph nodes
- Stage IV: cancer has spread to other organs
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TNM descriptors* [10]
*Adapted from the American Joint Committee on Cancer, 2002.
†In patients in whom pleural fluid was negative for tumor on multiple cytopathologic examinations, fluid is not bloody and is not an exudate. These patients should be further evaluated by video-assisted thoracoscopy and direct pleural biopsies. If the effusion is not related to the tumor, effusion should not be considered a staging element. The patient should be staged T1, T2 or T3.
Lung cancer staging* [10]
*Adapted from the American Joint Committee on Cancer, 2002.
Current therapies
The four primary treatment modalities used in the management of patients with NSCLC are: [11]
- Surgery
- Radiation therapy
- Combination chemotherapy
- Targeted therapy
Historically, surgical resection of small, localized tumors has provided the best chance for cure in patients with early-stage NSCLC. Surgical resection is usually possible in Stage I or II NSCLC and is possible for some patients with Stage IIIA NSCLC. If there is clinically evident nodal involvement (N2), surgery alone is not a curative option. [10,11]
Patients with advanced NSCLC (Stages IIIB and IV) have extensive invasion of local tissues (T4) or extensive nodal involvement (N3) and are considered inoperable. However, surgical resection of the primary tumor, in addition to radiation and/or chemotherapy, may be considered in some patients with advanced NSCLC to help ease tumor burden and relieve symptoms, offering improved quality of life and the potential for improved survival. [10,11]
Radiation therapy
Radiation therapy is used for the management of NSCLC in four major ways: [10-12]
- Primary therapy in early-stage disease in patients with medical contraindications to surgery such as poor performance status.
- Adjuvant therapy following surgery to achieve better local control.
- Primary therapy for unresectable disease, used with or without chemotherapy.
- Palliative therapy for the control of symptoms in Stage IIIB and Stage IV disease.
Chemotherapy can be used in all stages of NSCLC from early to advanced, but as a single modality, it is rarely curative in lung cancer patients. In early-stage NSCLC (Stage I or II), chemotherapy can be used in addition to surgery or radiation therapy as an attempt to cure the disease. Cisplatin/taxane-based combinations are used most often in first-line therapy, though some nonplatinum agents have proven to be effective. In advanced NSCLC (Stage IIIB or IV), single-agent chemotherapy is also used as a primary treatment modality. Treatment of late-stage NSCLC with chemotherapy is not considered curative but is intended to relieve symptoms and extend survival. [11]
Targeted therapy
Although platinum- and taxane-based chemotherapy regimens have been able to increase survival in patients with advanced NSCLC, the side effects of all chemotherapeutic agents—used alone or in combination—can be significant. [10]
Intensive research has led to new molecular and genetic understanding of cancer biology. Researchers are beginning to develop therapeutic agents that are able to target and kill cancer cells while sparing healthy cells. Targeted therapies offer the possibility of effective treatment with minimal
side effects. [10]
The development, growth and spread of cancer are regulated by specific cell surface receptors and molecular mediators. These receptors and growth-promoting molecules can be specifically targeted by new therapies. Such therapies have the potential to significantly improve survival rates without causing some of the major side effects of chemotherapy such as myelosuppression, neutropenia and neuropathy. [13,14]
Currently, the only targeted therapy approved for use in NSCLC is a HER1/EGFR tyrosine kinase inhibitor, erlotinib. [14] The human epidermal growth factor receptor (HER) family of tyrosine kinase (TK) receptors are a group of four closely related receptors (HER1/EGFR, HER2, HER3, HER4) that play a central role in cell division and cell death. [15]
Watch a video to see how a HER1/EGFR tyrosine kinase inhibitor works.
