Our knowledge of cancer is always expanding. Researchers and healthcare professionals take the knowledge gained from research studies and use it to develop better practices that will help prevent, detect and treat non–small cell lung cancer (NSCLC), as well as improve the quality of life of people with non–small cell lung cancer.
The following information is a selection of research showing promise for non–small cell lung cancer.
Risk reduction
Risk reduction strategies may reduce the chance of developing cancer. The best known way to reduce a person’s risk of developing lung cancer is to avoid all tobacco products and second-hand smoke.
Noteworthy research includes:
- A large European study found that people, including smokers, who eat a variety of fruit and vegetables may reduce their risk of developing lung cancer, particularly squamous cell lung cancer (Cancer, Epidemiology, Biomarkers & Prevention,PMID* 20807832; Cancer Causes & Control,PMID 19924549).
- Researchers have found that there may be a connection between nonsteroidal anti-inflammatory drugs (NSAIDs) and lung cancer development. Studies have shown that people who take aspirin have a lower risk of developing non–small cell lung cancer. Another NSAID, celecoxib (Celebrex), seems to reduce the risk in former smokers. More research is needed to determine whether aspirin and other NSAIDs could help prevent or reduce a person’s risk of developing lung cancer, and whether this affected by sex or current smoking status (Cancer Causes & Control, PMID 21987079; Clinical Lung Cancer, PMID 2183335; Cancer Prevention Research, PMID 21733822; Annals of Oncology, PMID 21385885).
Early detection
Researchers are working to improve early detection techniques for non–small cell lung cancer so that it can be found early, before signs and symptoms are noticed. This is important because the majority of people with non–small cell lung cancer are diagnosed with advanced disease.
Noteworthy research includes:
- Results from the National Lung Screening Trial suggest that screening with low-dose spiral (helical) computed tomography (CT) scan may reduce deaths from lung cancer (mortality) in people who were at high risk for developing the disease. The trial further showed that CT scan was a more effective screening tool than chest x-ray (Journal of Medical Screening, PMID 22045816; New England Journal of Medicine, PMID 21714641). More research is needed to determine how effective this type of screening will be in Canada.
- The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial examined the use of chest x-ray as a screening tool for lung cancer. The results of the study showed that annual screening with chest x-ray did not reduce deaths from lung cancer compared to regular medical examinations and care (JAMA, PMID 22031728).
- The NELSON trial in Europe is comparing screening for lung cancer with CT scans with no screening. The results are expected in 2015 (Cancer,PMID 18484588).
- The Pan-Canadian Early Lung Cancer Detection study is an ongoing study involving 8 centres across Canada. The main goal of the study is to see if several different techniques can detect lung cancer early. The techniques being studied include risk modelling, spiral CT, fluorescence bronchoscopy and blood biomarkers (proteins found in the blood that may be useful in finding cancer). Another goal of the study is to determine the cost of putting lung cancer screening into action in Canada. This study is currently recruiting participants and the results are expected in 2013 (National Cancer Institute [NCI] Clinical Trial).
- MicroRNA is short, single-stranded RNA. Doctors believe it regulates the expression of genes. MicroRNA is commonly changed in cancer cells. Scientists are looking at microRNA in sputum (material coughed up from the lungs) to see if it can help them detect non–small cell lung cancer early, before it causes any symptoms (Lung Cancer,PMID 19446359).
- Studies are looking to see if the body’s immune system response against abnormal proteins of cancer cells can be used to detect early lung cancer (Annals of Oncology,PMID 20675559).
- Fluorescence bronchoscopy uses a hand-held device or endoscope that gives off a blue or white light. This light helps doctors to identify changes in tissue fluorescence within the bronchi of the lungs. Normal tissue tends to fluoresce, or glow. Abnormal tissue tends to lose fluorescence.
- Meta-analysis suggested that autofluorescence bronchoscopy was more effective than white light bronchoscopy in finding precancerous tissue and lung cancer tumours (Lung Cancer, PMID 21237526; Journal of Thoracic Oncology, PMID 21642863).
- A large trial in the United Kingdom and another ongoing trial in Canada are studying people at high risk of developing lung cancer to see if cancer could be detected early with fluorescence bronchoscopy (National Cancer Institute [NCI] Clinical Trial). The results of these studies are not yet available.
Diagnosis
A key area of research activity involves developing better ways to diagnose and stage non–small cell lung cancer.
Noteworthy research includes:
- Researchers are studying endobronchial ultrasound (EBUS)with transbronchial needle aspiration as a new technique to diagnose and stage NSCLC. Doctors believe EBUS may eventually replace mediastinoscopy, a diagnostic procedure that looks for lung cancer that has spread to the lymph nodes in the chest. EBUS is less invasive than mediastinoscopy. During EBUS, the doctor puts a small ultrasound probe attached to a bronchoscope (a type of endoscope) into the trachea and bronchi. Doctors can pass a hollow needle through the bronchoscope to take a sample cells from nearby lymph nodes in the chest (Thorax,PMID 19454408; Journal of Thoracic and Cardiovascular Surgery, PMID 22154791; European Journal of Cardiothoracic Surgery,PMID 20022761, PMID 18952453).
- If EBUS does not find cancer, a follow-up mediastinoscopy may be done to ensure cancer has not spread to the nearby lymph nodes (Current Opinion in Pulmonary Medicine,PMID 19395972).
- EBUS is sometimes combined with endoscopic esophageal ultrasound. Like EBUS, endoscopic esophageal ultrasound uses a small ultrasound probe attached to an endoscope that is inserted into the esophagus. The esophagus is located behind the trachea (wind pipe) and is also near some of the lymph nodes in the chest. If a suspicious area is found, doctors can pass a hollow needle through the endoscope to sample nearby lymph nodes (Seminars in Respiratory and Critical Care Medicine, PMID 21500125; Annals of Thoracic Surgery,PMID 20667324; JAMA,PMID 18252884).
- Researchers are looking into how combined positron emission tomographyandcomputed tomography(PET/CT) may be used to help stage NSCLC. Research has shown that PET/CT better identifies people with inoperable NSCLC than regular staging techniques. As a result, PET/CT helped to reduce the number of unnecessary thoracotomies. However, PET/CT did not affect overall survival. One of the problems with PET/CT is that it may give false positive results. This means that it may indicate that cancer has spread to an area of the body when it hasn’t (Annals of Internal Medicine,PMID 19581636; New England Journal of Medicine,PMID 19571281).
- Virtual bronchoscopy is a type of imaging test that uses a CT scan to create images of the inside of the bronchi without having to insert an endoscope. Researchers recently studied virtual bronchoscopy in combination with a tiny ultrasound probe in people with lung cancer in the outer part of the lung (peripheral lung). They wanted to see if it was a useful tool for finding lung cancer that cannot be reached by a regular bronchoscope (endoscope that is used to look at the inside of the bronchi). Virtual bronchoscopy also helps doctors guide a biopsy needle to take a sample of tissue from abnormal-looking areas of the lung found by a CT scan (European Journal of Radiology,PMID 20022191).
- Virtual bronchoscopy with PET/CT may detect regional lymph nodes metastases. IT also provides images of the bronchi in the outer parts of the lung (Journal of Nuclear Medicine, PMID 21908390).
Prognostic factors
Prognostic factors that may help determine the outcome of the disease are being studied in non–small cell lung cancer. They can be used to predict the chances of recovery or of cancer coming back. Doctors may also use prognostic factors to help them make treatment recommendations.
Noteworthy research includes:
- People with early stage non–small cell lung cancer who quit smoking after their diagnosis had improved survival compared to those who continued to smoke after they were diagnosed. A recent review of the evidence shows not smoking after a diagnosis of early stage NSCLC improves prognostic outcomes (British Medical Journal,PMID 20093278).
- A recent review of trial results has suggested that non-smokers may get more benefits from epidermal growth factor receptor (EGFR) targeted therapy than smokers, especially people who have been previously treated with chemotherapy. More study is needed to determine if smoking history is a predictor of response to chemotherapy in non–small cell lung cancer (Clinical Lung Cancer, PMID 22154074).
- More copies of the EGFR gene are associated with a better survival in people treated with the targeted chemotherapy drugs gefitinib (Iressa) or erlotinib (Tarceva). Better survival appears to be limited to people who are of non-Asian descent (Annals of Oncology, PMID 20826716).
- Gene expression profiling may help doctors predict tumour behaviour and identify people with NSCLC who may have a better or worse prognosis. It may also help doctors predict which NSCLC will respond better or worse to certain types of treatment, such as chemotherapy. Furthermore, certain genes may be used as specific markers for NSCLC. These genes could potentially be used to develop new treatments for the disease (Journal of Clinical Oncology,PMID 20823422).
- VDAC1 (voltage-dependent anion channel 1) is related to cell functions that need energy to be done. Too much (overexpression) of the VDAC1 gene is associated with aggressive tumours that grow and spread quickly into the surrounding tissue. This overexpression is also a predictor of poor outcome with non–small cell lung cancer (PLoS One, PMID 21297950).
- Inactive (methylated) forms of the RASSF1A tumour suppressor gene may predict poor survival for surgically treated non–small cell lung cancer (Carcinogenesis, PMID 21156971).
- Polymorphisms are changes to the DNA of a gene. Researchers found that certain types of polymorphisms in GSTM1 and CYP1A1 help predict response to chemotherapy for non–small cell lung cancer. People who had tumours that had deficient-type GSTM1 responded better to platinum drugs, such as cisplatin (Platinol AQ). People with tumours that had changes to CYP1A1 responded better to non-platinum drugs, such as gemcitabine (Gemzar) or docetaxel (Taxotere). More research is needed to determine if these gene changes may direct treatment options in the future (Lung, PMID 22109568).
- MicroRNA may help doctors tell subtypes of NSCLC apart. Researchers have found that some subtypes of NSCLC have a higher risk of side effects with certain treatments, such as targeted therapy. Knowing what subtype of NSCLC a person has may help doctors predict how a person will respond to a particular type of treatment (Clinical Cancer Research,PMID 20068076; Journal of Clinical Oncology,PMID 19273703).
- Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) are tumour markers. Researchers are studying these tumour markers in people with NSCLC. Normal levels of CEA or CYFRA 21-1 are associated with a more favourable prognosis (Anticancer Research,PMID 20683062).
Treatment
Researchers are looking for new ways to improve the treatment of non–small cell lung cancer. Advances in cancer treatment and new ways to manage the side effects related to treatment have improved the outlook and quality of life for many people with cancer.
Noteworthy research includes:
- Video-assisted thoracic surgery (VATS) is a surgical technique that doctors sometimes use to remove small lung tumours or the lobe of a lung (lobectomy) that contains a tumour. A Canadian study found that small metal coils inserted into the lung with the help of a CT scan may be useful guides for doctors performing VATS (Radiology,PMID 19188326). VATS is a less invasive procedure than thoracotomy, but this specialized technique may not be available in all hospitals where lung cancer surgery is performed. Recently, a phase III trial found that people who had VATS had fewer breathing-related complications and a shorter hospital stay compared to those who had a thoracotomy (Journal of Thoracic and Cardiovascular Surgery,PMID 20172539).
- Robotic surgery uses the same video-assisted techniques as VATS to control robotic arms to move instruments during surgery. Studies looking at using robotic surgery for a lobectomy have shown that it is safe. People who had robotic lung surgery had shorter hospital stays and similar survival rates as thoracotomy (Seminars in Thoracic Cardiovascular Surgery, PMID 21807297, PMID 22104677).
- Cancer vaccines are an exciting area of research in NSCLC treatment. Cancer vaccines are designed to stimulate the body to produce an immune response against cancer cells. Ongoing clinical trials are trying to find out if vaccine therapy is a good way to treat NSCLC (Annals of Oncology, PMID 22156658; Critical Reviews in Oncology Hematology, PMID 22366114).
- Radiofrequency ablation (RFA) is a procedure that uses a high-frequency electrical current to destroy cancer cells. Percutaneous RFA is a technique that may be used to treat people with non–small cell lung cancer or other types of primary cancer that has spread to the lungs. Percutaneous RFA involves using a needle to pass an electric current through the skin and into a tumour in the lung. Doctors may consider using this treatment for people with NSCLC who can’t have surgery or radiation therapy. RFA is not meant to replace surgery if the person is a good surgical candidate. (European Journal of Radiology, PMID 21310562; Journal of Thoracic Oncology, PMID 22052222; Insights into Imaging, PMID 22347976). This technique may be most useful for lung tumours that are 3 cm or less in size.
- Between 15% and 20% of people with non–small cell lung cancer will eventually develop brain metastases. Prophylactic cranial irradiation (PCI) is radiation therapy given to the whole brain to prevent brain metastases. PCI may cause side effects that can affect quality of life. A recent trial that included Canadian researchers showed that PCI may reduce the number of brain metastases, but it does not improve overall survival and causes a significant decline in memory (Journal of Clinical Oncology, PMID 21135267, PMID 21135270). Research continues to try to identify the people with non–small cell lung cancer who are at highest risk for developing brain metastases and would benefit from PCI (Cancer Management and Research, PMID 21931502).
- Researchers studied stereotactic radiosurgery plus whole-brain radiation therapy in a small group of people with NSCLC whose cancer had spread to the brain. This treatment was well tolerated and effective for treating up to 3 brain metastases (Anticancer Research,PMID 20683055). Researchers are now looking at Gamma Knife as a way of delivering stereotactic radiosurgery, with or without whole-brain radiation therapy, in people with NSCLC that has spread to the brain (International Journal of Radiation Oncology, Biology, and Physics, PMID 21530098; Progress in Neurological Surgery, PMID 22236676). A recent study found that people who received Gamma Knife radiosurgery earlier in the day had a more favourable outcome compared to those that received treatment later in the day. This observation may be related to natural body cycles (circadian rhythms) of growth and repair that have recently been studied in people undergoing radiation therapy. It is thought that cells may respond better to radiation therapy at certain times of the day (Cancer,PMID 20830691).
- Stereotactic body radiotherapy uses the same techniques as stereotactic radiosurgery, but it treats other parts of the body than the brain. Researchers are looking at using stereotactic body radiotherapy to treat early stage (stage I) non–small cell lung cancer that is found in the outer parts of the lung for people who cannot have surgery. Some trials have shown that the treatment offers local control of the tumour (Current Oncology Reports, PMID 20446066; Radiotherapy and Oncology, PMID 22265734). More research is needed to understand the role, safety and effectiveness with this technique (Journal of Thoracic Diseases, PMID 22263087).
- Chemotherapy before surgery (preoperative chemotherapy) may shrink non–small cell tumours and make surgery to remove them more successful. A phase III study found that giving cisplatin (Platinol AQ) and gemcitabine (Gemzar) before surgery improved survival in people diagnosed with stage IIB and IIIA non–small cell lung cancer, but it did not improve survival in people with stage IB (Journal of Clinical Oncology, PMID 22124104).
- Researchers are studying new chemotherapy drugs for their effectiveness with non–small cell lung cancer.
- Crizotinib is a new drug that targets non–small cell lung cancers with changes to the anaplastic lymphoma kinase (ALK) gene. The ALK gene is involved in regulating cell growth. Studies have shown that the drug works in people who have ALK-positive adenocarcinoma tumours of the lung (Lancet Oncology, PMID 21933749; Journal of the National Comprehensive Cancer Network, PMID 22157554; Drug Design Development and Therapy, PMID 22162641). It has been approved in the United States for treatment of ALK-rearranged non–small cell lung cancer, but has not yet been approved in Canada.
- Nedaplatin (Aqupla) is a platinum-based drug similar to cisplatin, which is used for non–small cell lung cancer. A recent meta-analysis showed that nedaplatin combined with irinotecan (Camptosar) improved survival time in people with squamous cell forms of non–small cell lung cancer. More research is needed to confirm these findings (Journal of Thoracic Oncology, PMID 21150472).
- Cetuximab (Erbitux) targets overexpression of the epidermal growth factor receptor (EGFR) in cancer cells. Several clinical trials have suggested that cetuximab may improve survival in people with advanced or recurrent non–small cell lung cancer, when the drug combined with other chemotherapy drugs currently being used to treat the disease. Research continues to examine the role of cetuximab in the treatment of non–small cell lung cancer (Expert Reviews in Anticancer Therapy, PMID 22316364; Lung, PMID 21424607; European Journal of Clinical Pharmacology, PMID 21207017).
- There are concerns around treating people older than 70 years of age with chemotherapy for non–small cell lung cancer. It was thought that this group could not tolerate the side effects and that it did not improve survival from the disease. Studies have shown that older people with NSCLC do experience more severe side effects from chemotherapy, but their disease responds to the chemotherapy and survival is improved (Annals of Oncology, PMID 21393380; The Lancet, PMID 21831418). Clinical trials designed to examine chemotherapy in older people with non–small cell lung cancer are need to find the best treatments for this age group.
Supportive care
Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects.
Noteworthy research includes:
- People diagnosed with metastatic NSCLC may benefit from early palliative care. American researchers found that people who were given palliative care along with standard care at the time of diagnosis had a better quality of life and outlook. They also survived longer than those who were only given standard care. In addition, people who received early palliative care also needed less aggressive care at the end of life to control symptoms compared to those given only standard care (New England Journal of Medicine,PMID 20818875).
- People with NSCLC may benefit from taking palonosetron (Aloxi). Researchers are studying this drug’s ability to prevent nausea and vomiting in people undergoing chemotherapy. A study found that people with stage II–IV NSCLC who were being treated with chemotherapy had less nausea and vomiting when also given palonosetron than those who did not receive this drug (Medical Oncology, PMID 20602263). Another study compared palonosetron with ondansetron (Zofran). This study found that people given palonosetron experienced less nausea and vomiting from chemotherapy (Supportive Care in Cancer, PMID 21761096).
- Researchers reviewed the role of exercise to improve quality of life in people living with non–small cell lung cancer (Lung Cancer, PMID 21316790). Exercise programs may improve a person’s ability to do exercise, but it is not sure if this improves quality of life. A recent study suggested that while strength training helped improve strength in the legs, exercise had no effect on quality of life or increased the distance walked in 6 minutes (Lung Cancer,PMID 20541832). Another study had similar conclusions, while noting that many people dropped out of the exercise program or discontinued it at home after the program ended (Acta Oncologica, PMID 21231792).
*PMID is the National Library of Medicine PubMed abstract identity number.
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