- In men, the highest age-standardised incidence rates for lung cancer are observed in Central and Eastern Europe (53.5 per 100,000) and Eastern Asia (50.4 per 100,000)1, Central-Eastern and Southern Europe (48.5–56.5 per 100,000)1
- In women, lung cancer age-standardised incidence rates are highest in North America (33.8 per 100,000) and Northern Europe (35.8–37.0 per 100,000)1
- Only 15% of lung cancers are detected when the tumour is in the early stage,2 which
impact on survival rates:
5-yearsurvival rate of patients with lung cancer in the US is 17.8%3
- The median age of lung cancer diagnosis is 70 years and has been increasing over time4
(Click here for slides on NSCLC: epidemiology)
There are two main types of lung cancer:
1. Small cell lung cancer (SCLC)
Overall, 13.2% of all lung cancers are classified as small cell lung cancer (SCLC).3 This form of lung cancer is characterised by small, round cancerous cells with an enlarged nucleus and minimal cytoplasm.6 SCLC is classed as either limited disease (LD) or extensive disease (ED). Prognosis is generally poor, with overall survival rates at 5 years of up to 10%. However, patients with LD have a marginally more favourable prognosis than those with ED, with a 5-year survival rate of 14% reported in patients with LD.7,8
2. Non-small cell lung cancer (NSCLC)
NSCLC is the most common form of lung cancer, responsible for over 83.6% of lung cancer cases.3 There are three main subtypes of NSCLC:
- Adenocarcinoma (45.0% of NSCLC cases3) is the most common form of lung cancer and the most common subtype of NSCLC. It develops in the mucus-secreting glands in the lining of the airways.9 Approximately 10% of Western and up to 50% of Asian patients with adenocarcinoma have epidermal growth factor receptor (EGFR) mutations.10 This subgroup of patients may benefit from targeted therapies, including EGFR inhibition by tyrosine kinase inhibitors (TKIs) or ErbB Family Blockers.
Squamous cell carcinoma (SqCC; 23.0% of NSCLC cases)3 develops in the squamous
cells that line
the airways and tends to spread locally. It is often caused by smoking, and has limited
treatment options. Patients with SqCC are typically treated with
platinum-basedchemotherapy, which is standard first-line therapy. With the increasing understanding and determination of specific biomarkers, identifying a molecular target for SqCC is of key importance. EGFR mutations are rarely (<5%) found in SqCC, however, expression of wild-type EGFR tends to be high. Studies with patients with SqCC treated with EGFR tyrosine kinase inhibitors (TKIs) have shown improved clinical outcomes, which has led to the approval of the EGFR TKIs erlotinib and afatinib as second-linetherapy.10,11
- Large cell carcinoma (1.8% of NSCLC cases)3 is characterised by large, rounded cells that are seen when cancerous tissue is examined microscopically.12,13 This type of tumour lacks squamous or glandular differentiation and is therefore also known as undifferentiated carcinoma.13
The remaining cases of NSCLC include rarer subtypes, such as adenosquamous carcinoma and sarcomatoid carcinoma, and cases where the subtype is unknown.3
Fig. 1: Subtypes of NSCLC
Source: Howlader et al. SEER Cancer Stats Review
(Click here for slides on NSCLC: epidemiology)
Prognosis and treatment for NSCLC
Prognosis and treatment for NSCLC is dependent on the stage of the disease.
- In patients with
early-stageNSCLC, surgical resection (usually lobectomy) is considered the most suitable treatment choice14
- In multiple trials it has been demonstrated that overall survival is superior in patients with resectable stage I to IIIA NSCLC who undergo resection and complete mediastinal lymph node dissection, compared with patients who undergo resection and lymph node sampling (hazard ratio 0.63; 95% confidence interval 0.51–0.78; p≤0.0001)14
- Stage III (late-stage) tumours can be successfully treated in some cases, but cure rates are
much lower than in
early-stageNSCLC. Patients with Stage IIIA and selected Stage IIIB disease have a poor 5-yearsurvival rate (5–30%) with surgery alone, thus these patients should be offered surgery in addition to adjuvant therapy.15
Smoking accounts for almost 30% of all cancer deaths in patients with lung cancer; it is responsible
for 87% deaths in men and 70% of deaths in women.18 At least 50 carcinogens have been
tobacco smoke.19 A causal association with lung cancer has also been shown for
cigars, cigarillos, pipes, bidis and water pipes.20 Although there is an approximate
increase in lung cancer risk for smokers compared with
The signs and symptoms of lung cancer may take many years to appear, are usually
Owing to the
A wide range of diagnostic procedures are used to diagnose lung cancer including:30
Baseline blood tests, which include renal and liver function tests (LFTs) and tests for calcium and lactate dehydrogenase (LDH) levels, can indicate the existence and severity of acute or chronic tissue damage.
Samples of sputum are not routinely used for all patients. These tests are usually performed for patients with centrally located nodules or masses and who are unable to tolerate or do not want to undergo bronchoscopy.
Cells or tissues are removed from the lungs and examined microscopically to make a definitive diagnosis of cancer. If the cells are cancerous, they may be studied further to detect the rate of growth and extent of the cancer. Common biopsy techniques include:31
- Transbronchial biopsy – A bronchoscope (thin viewing instrument) is inserted orally into the windpipe to examine the bronchi and lungs, and a tissue sample is taken
- Needle biopsy – After a local anaesthetic has been given, and with the aid of CT scans or fluoroscopy, a needle is guided through the chest wall to obtain a tissue sample
- Thoracoscopic (or
video-assisted– After a general anaesthetic has been given, an endoscope is inserted through the chest wall into the chest cavity. Biopsy tools can then be inserted through the endoscope thoracic surgery [VATS]) biopsy
- Open biopsy – After a general anaesthetic has been given, an incision is made in the skin on the chest and a piece of lung tissue is surgically removed.
- Liquid biopsy – Minimally invasive techniques, such as exfoliative cytology and aspiration cytology, may be used in patients with advanced disease.32 In addition, the use of surrogate sources of DNA, such as blood, serum and plasma samples, which often contain circulating free tumour DNA or circulating tumour cells, is emerging as a new strategy, referred to as ‘liquid biopsy’32
Cancerous cells or tissue obtained by biopsy or surgery are examined to determine the histology of the lung cancer. The morphology and cell characteristics may be examined and their responses to antibodies and immunohistochemical markers evaluated.34
Cancer stage refers to the size and/or extent of the original (primary) tumour and the spread of
cancer cells in the body. The stages are listed in the table 1 within available treatment options. The grade of a cancer
describes a tumour based on the morphology of the tumour cells under a microscope. Cancers are
graded as low-, intermediate- or
Tumour samples are tested for various biomarkers, using techniques such as genome sequencing to
detect mutations or rearrangements in DNA. Current clinical guidelines recommend that all patients
with NSCLC be tested for EGFR (ErbB1) mutations and ALK rearrangements.10,22,36 Biomarker
the time of diagnosis is becoming increasingly important with the availability of therapies targeted
In some forms of cancer, the levels of biomarkers can provide an indication of the stage of a tumour and the prognosis.37
Three main types of treatment are used in the management of lung cancer, which can be used as monotherapies or in combination are surgery; radiotherapy; and systemic therapy, which includes chemotherapy and targeted therapy.38 The stage of a patient’s cancer determines the treatment approach (Table 1).38 For patients with advanced or metastatic NSCLC, there is a high unmet medical need for clinically effective and well‑tolerated therapies.39 Most patients with advanced or metastatic lung cancer are treated with chemotherapy regimens that provide an overall survival of less than one year, and are associated with a variety of adverse effects.39
Table 1: Treatment is dependent on cancer stage
Cancer is present only in one part of the lung and has not spread to the lymph nodes.
The tumour can often be removed with surgery. Chemotherapy is sometimes used after
surgery (adjuvant chemotherapy) to reduce the chance of recurrence. Chemotherapy and/or
radiotherapy may sometimes be given before surgery to shrink the tumour; this is known
Cancer has spread to nearby lymph nodes or nearby tissues, e.g. chest wall.
It may also be possible to remove stage II NSCLC with surgery, and chemotherapy or radiotherapy is often given following surgery to reduce the risk of recurrence.
Cancer has spread more extensively within the chest and, generally, to the major lymph nodes. Large tumours have invaded surrounding organs and lymph nodes outside the chest.
Although surgery may be considered as an option at this stage, this is often not possible because the cancer may have spread too far. Chemotherapy, on its own or combined with radiotherapy, may be given before an operation. If surgery is not possible, radiotherapy can be given instead. In some cases, chemotherapy given on its own, or in combination with radiotherapy, will be the only treatment used. For some patients with locally advanced or metastatic NSCLC, newer targeted treatments may also be used.
Cancer has spread (metastasised) to distant parts of the body, e.g. to the liver or bones.
Cancer has spread (metastasised) to distant parts of the body, e.g. to the liver or bones The aim is to control symptoms and maintain a good quality of life for as long as possible. Radiotherapy may be used to shrink the cancer and reduce symptoms such as pain. Chemotherapy may be given before or after radiotherapy, and may shrink the cancer and improve quality of life for some people. For some patients with locally advanced or metastatic NSCLC, newer targeted treatments may also be used.
Treatments that target specific molecular markers or structures in tumour cells are increasingly becoming available. These treatments have developed as a result of a greater understanding of the molecular biology and pathogenesis of NSCLC. In particular, two processes have been identified as major contributors to the pathology of NSCLC: tumour cell signal transduction and tumour angiogenesis.40,41
In tumour cells, elements of signal transduction pathways are often mutated or overexpressed relative
to normal cells. An important group of signal transduction elements in tumour cells is the ErbB
Family of receptors.42 In NSCLC, genetic mutations may occur, most commonly in the EGFR
gene, which dysregulate
Afatinib (GIOTRIF®)* is the first irreversible ErbB Family Blocker that inhibits
signalling from all
ErbB Family receptors. Afatinib is approved for use in patients with EGFR
Angiogenesis is an essential process for normal growth and development, including for functions such
as embryonic development, wound healing and restoring blood flow to damaged tissues. However, it is
also vital for tumours to grow and spread to other organs. The development of new blood vessels in
tumours requires the interaction of growth factors, such as fibroblast growth factor (FGF),
Approximately 25% of patients with advanced NSCLC show disease progression after the initial cycle
of first-line chemotherapy, and most patients will eventually experience relapse and require
subsequent therapy.50 Despite a significant amount of research in this area, there have
been no new
treatments for these patients for some time and until recently, no combination regimens were
available in this
By focusing on the molecular and cellular changes that are specific to the cancer, targeted
therapies may be more effective than current treatments and less harmful to normal cells, thereby
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