NON-SMALL CELL LUNG CANCER (NSCLC) PRESENTED BY: SYAZRIL EFFANDY BIN ISMAIL FARAH DIYANA BT HISHAMUDDIN SUPERVISOR: MADAM ROS IDAYU BT MAT NAWI
INTRODUCTION TO LUNG CANCER ANATOMY OF LUNGS • In chest, have two sponge-like organs called lungs. Right lung is divided into three sections known as lobes. Left lung is divided into two lobes. Because the heart takes up more space on that side of the body, the left lung is smaller. • The trachea divides into bronchi, which enter the lungs and divide further into smaller bronchi. These divide into smaller branches known as bronchioles. Alveoli are tiny air sacs located at the end of the bronchioles.
CONT’S.. WHAT IS LUNG CANCER? • Lung cancer is a disease that develops as a result of uncontrolled cell division in the lungs. Cells divide and replicate themselves as part of their normal function. • Damaged cells dividing uncontrollably create masses, or tumors, of tissue that eventually keep your organs from working properly. • Lung cancer is the name for cancers that start in lungs — usually in the airways (bronchi or bronchioles) or small air sacs (alveoli).
CONT’S.. • Cancers that begin elsewhere and spread to lungs are usually named after the location where they begin. It may refer to this as cancer that’s metastatic to lungs. • There are many cancers that affect the lungs, but the term "lung cancer" usually refers to two types: non-small cell lung cancer and small cell lung cancer.
EPIDEMIOLOGY • Lung cancer is one of the most common types of cancer in Malaysia, accounting for about 10% of all cancers. • Lung cancer is the most common cause of cancer-related death in Malaysia • The survival rate of lung cancer patients in Malaysia at 1 and 5 years is one of the poorest compared to other cancer types. • Male Malaysian have a lifetime risk of about 1in 55. Male Chinese have the highest risk, followed by Malay and Indians. The risk is about 1 in 135 for women. Lung cancer in Malaysia. Journal of Thoracic Oncology. Retrieved March 18, 2023.
CONT’S.. • In 2018, 2,094,000 new cases of lung cancer were diagnosed worldwide, making lung cancer the leading cause of cancer death. • there were an estimated 229,000 new cases of lung cancer in the US in 2020, accounting for 12.7% of all cancer diagnoses Barsouk, A. (2021). Epidemiology of Lung Cancer. Contemporary oncology (Poznan, Poland).
NON SMALL CELL CARCINOMA • About 80% to 85% of lung cancers are NSCLC • Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It accounts for over 80% of lung cancer cases • Common types include adenocarcinoma, squamous cell carcinoma and Large cell (undifferentiated) carcinoma. • Adenosquamous carcinoma and sarcomatoid carcinoma are two less common types of NSCLC.
ETIOLOGY • Tobacco and smoking. Tobacco smoke damages cells in the lungs, causing the cells to grow abnormally. • Asbestos. These are hair-like crystals found in many types of rock and are often used as fireproof insulation in buildings. When asbestos fibers are inhaled, they can irritate the lungs. • Radon. This is an invisible, odorless gas naturally released by some soil and rocks. • Air pollution. Research has found that exposure to outdoor air pollution can lead to lung cancer. Common causes of pollution include transportation and industrial fumes, power generation, and smoke from intentional burning and wildfires.
CONT’S.. • Other substances. Other substances such as gases or chemicals at work or in the environment can increase a person’s risk of developing lung cancer. • Genetics. Some people have a genetic predisposition for lung cancer.
CONT’S.. a) Squamous cell carcinoma • Squamous cell carcinomas start in squamous cells, which are flat cells that line the inside of the airways in the lungs. • They are often linked to a history of smoking and tend to be found in the central part of the lungs, near a main airway (bronchus). • Also called epidermoid carcinoma • About 30% of all NSCLC case are squamous cell carcinoma • It is more difficult to treat if cancer spread to other areas of the body.
CONT’S.. b) Adenocarcinoma • Adenocarcinomas start in the cells that would normally secrete substances such as mucus • Adenocarcinoma is usually found in the outer parts of the lung and is more likely to be found before it has spread. • Usually begins in the epithelial cell • People with a type of adenocarcinoma called adenocarcinoma in situ (previously called bronchioloalveolar carcinoma)
CONT’S.. c) Large cell carcinoma • Named because of the large size of the cancer cells that can be seen under microscope. • Large cell carcinoma can appear in any part of the lung. • It tends to grow and spread quickly, which can make it harder to treat. A subtype of large cell carcinoma, known as large cell neuroendocrine carcinoma (LCNEC), is a fastgrowing cancer that is very similar to small cell lung cancer.
SIGN AND SYMPTOM • Coughing that gets worse or doesn’t go away. • Chest pain. • Shortness of breath. • Wheezing. • Coughing up blood. • Feeling very tired all the time. • Weight loss with no known cause. • Worsening cough. • Hemoptysis. • Malaise. • Dyspnea. • Hoarseness.
DIAGNOSTICS • Chest x-ray- A low doses of radiation use to make images of structures inside your body • CT-Scan- A powerful x-rays that make a detailed picture of the tissue and the blood vessel in the lung. • MRI- A procedure that’s uses a magnet radiation and shown blood flow, organs and structure.
CONT’S.. • Fine needle aspiration- The removal of tissue or fluid from the lung to loo for cancer cell. • Sputum cytology - A lab test to check the mucus from cough that maybe containing a cancer cell. • Bronchoscopy- A procedure to look inside the trachea and large ariways in the lung for abnormal areas and using tools to take a biopsy. • Thoracentesis- The use of a needle to remove fluid from the space between the lining of the chest and the lung. A pathologist examines the fluid under a microscope to look for cancer cells.
STAGING
CONT’S.. Stage 0 (in-situ): Cancer is in the top lining of the lung or bronchus. It hasn’t spread to other parts of the lung or outside of the lung. Stage I: Cancer hasn’t spread outside the lung. Stage II: Cancer is larger than Stage I, has spread to lymph nodes inside the lung, or there’s more than one tumor in the same lobe of the lung. Stage III: Cancer is larger than Stage II, has spread to nearby lymph nodes or structures or there’s more than one tumor in a different lobe of the same lung. Stage IV: Cancer has spread to the other lung, the fluid around the lung, the fluid around the heart or distant organs. Each stage has several combinations of size and spread that can fall into that category. For instance, the primary tumor in a Stage III cancer could be smaller than in a Stage II cancer, but other factors put it at a more advanced stage. The general staging for lung cancer is;
• NSCLC is classified according to the TNM system suggested by the American Joint Committee on Cancer (AJCC). The staging system takes into account the primary tumor characteristics (T1-T4, see table below), lymph nodes involvement (N0-N3, see table below), and the presence (M1) or absence (M0) of distant metastasis.
TREATMENT AND MANAGEMENT
1. SURGERY • Surgery to remove the cancer might be an option for early-stage non-small cell lung cancer (NSCLC). It provides the best chance to cure the disease • The goal of surgery is to completely remove the lung tumor and the nearby lymph nodes in the chest. • Lung cancer surgery is a complex operation that can have serious consequences, so it should be done by a surgeon who has a lot of experience operating on lung cancers. • The type of operation recommends depends on the size and location of the tumor and on how well lungs are functioning.
CONT’S.. Types of surgery: i) Lobectomy • The lungs are made up of 5 lobes (3 on the right and 2 on the left). In this surgery, the entire lobe containing the tumor(s) is removed. If it can be done, this is often the preferred type of operation for NSCLC. ii) A wedge resection • If the surgeon cannot remove an entire lobe of the lung, the surgeon can remove the tumor, surrounded by a margin of the healthy lung.
CONT’S.. iii) Segmentectomy • The surgeon removes the portion of the lung where the cancer developed. Typically, more lung tissue and lymph nodes are removed during a segmentectomy compared to a wedge resection. iv) Pneumonectomy • This surgery removes an entire lung. This might be needed if the tumor is close to the center of the chest.
2. RADIATION THERAPY • Radiation therapy uses powerful X-ray beams to kill cancer cells or keep them from growing.
CONT’S.. • In people with NSCLC, brachytherapy is sometimes used to shrink tumors in the airway to relieve symptoms which is radiation given from a machine outside the body. • The most common type of radiation is intensity modulated radiation therapy (IMRT). • For some people, their tumors require a specialized type of radiation such as stereotactic body radiation therapy (SBRT) or proton therapy.
CONT’S.. • These types of radiation therapy use CT scans or PET scans to plan out exactly where to direct the radiation beam to lower the risk of damaging healthy parts of the body. It is not an option for all patients, but it may be used for early-stage disease and for a small tumor when surgery is not an option. • Some people with stage I NSCLC or people who cannot have surgery may be treated with stereotactic radiation therapy instead of surgery.
3. CHEMOTHERAPY • Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. • It has been shown to improve both the length and quality of life for people with lung cancer of all stages • When adjuvant chemotherapy is given after surgery, it is usually given for a shorter period of time (such as 4 cycles) than for those with stage IV lung cancer. • Common drugs used to treat lung cancer include either 2 or 3 drugs given together or 1 drug given by itself.
CONT’S.. The chemo drugs most often used for NSCLC include: • Cisplatin • Carboplatin • Paclitaxel (Taxol) • Albumin-bound paclitaxel (nab-paclitaxel, Abraxane) • Docetaxel (Taxotere) • Gemcitabine (Gemzar) • Vinorelbine (Navelbine) • Etoposide (VP-16) • Pemetrexed (Alimta)
4. TARGETED THERAPY • Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. • This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. • Not all tumors have the same targets. To find the most effective treatment, may run tests to identify the genes, proteins, and other factors in the tumor. • For some lung cancers, abnormal proteins are found in unusually large amounts in the cancer cells.
CONT’S.. Drugs that target tumor blood vessel growth (angiogenesis) • Bevacizumab (Avastin) is used to treat advanced NSCLC. It is a monoclonal antibody (a lab-made version of a specific immune system protein) that targets vascular endothelial growth factor (VEGF), a protein that helps new blood vessels to form. • Ramucirumab (Cyramza) can also be used to treat advanced NSCLC. This drug is a monoclonal antibody that targets a VEGF receptor (protein). It helps stop the formation of new blood vessels.
CONT’S.. Drugs that target cells with KRAS gene changes • Some NSCLCs have changes in the KRAS gene that cause them to make an abnormal form of the KRAS protein. This abnormal protein helps the cancer cells grow and spread. • Sotorasib (Lumakras) and adagrasib (Krazati) are drugs known as KRAS inhibitors. They work by attaching to the KRAS G12C protein, which helps keep cancer cells from growing.
CONT’S.. Drugs that target cells with EGFR gene changes • Epidermal growth factor receptor (EGFR) is a protein on the surface of cells. It normally helps the cells grow and divide. Sometimes NSCLC cells have too much EGFR, which makes them grow faster. • EGFR inhibitors used in NSCLC with EGFR gene mutations Erlotinib (Tarceva) Afatinib (Gilotrif) Gefitinib (Iressa) Osimertinib (Tagrisso) Dacomitinib (Vizimpro)
5. IMMUNOTHERAPY • Immunotherapy uses the body's natural defenses to fight cancer by improving immune system's ability to attack cancer cells. • People who receive treatment using immunotherapy for NSCLC may receive only 1 drug, a combination of immunotherapy drugs, or it may be combined with chemotherapy.
CONT’S.. There are different ways immunotherapy can use the body's immune system to treat cancer: Drugs that block the PD-1 pathway. The PD-1 pathway may be very important in the immune system's ability to control cancer growth. Blocking this pathway with PD-1 and PD-L1 antibodies has stopped or slowed the growth of NSCLC for some patients. • Atezolizumab (Tecentriq) • Durvalumab (Imfinzi) • Cemiplimab-rwlc (Libtayo) • Nivolumab (Opdivo) • Pembrolizumab (Keytruda)
CONT’S.. Drugs that block the CTLA-4 pathway. Another immune pathway that may be targeted is the CTLA-4 pathway. • Ipilimumab (Yervoy) and tremelimumab (Imjudo) are also drugs that boost the immune response, but they block CTLA-4, another protein on T cells that normally helps keep them in check. • These drugs are used along with a PD-1 inhibitor (ipilimumab with nivolumab, and tremelimumab with durvalumab); they are not used alone.
CASE STUDY
CONT’S.. NAME Mrs J AGE 71 year old GENDER Female MEDICAL HISTORY No significant past medical history SIGN AND SYPTOM • Presented 4 and a half years ago with a weight loss of about 50 pounds over six months prior to presentation. • Complained of occasional shortness of breath but denied any cough. PHYSICAL EXAMINATION Revealed enlarged right axillary and supraclavicular lymph nodes.
CONT’S.. INVESTIGATION AND FINDINGS • Mammography- multiple enlarged right axillary lymph nodes, but no suspicious lesions were seen in either breast • Ultrasound-guided core biopsy of the right axillary lymph node- Report showed poorly differentiated metastatic adenocarcinoma.
CONT’S.. • Computed tomogram (CT) of the chest with contrast- There were multiple irregular nodular opacities in bilateral lungs, with the largest measuring 10 mm, and extensive bilateral mediastinal lymphadenopathy and supraclavicular lymphadenopathy, with the largest measuring 1.8 cm (Figures 1-3). Figure 1: CT chest lung window showing right upper lobe nodule on 06/12/2017 Figure 2: CT chest soft tissue window showing right subclavian lymph nodes, with the largest measuring 19.54 mm, on 06/12/2017 Figure 3: CT chest soft tissue window showing right axillary lymph nodes (marked with a black circle) on 06/12/2017
CONT’S.. • Magnetic resonance imaging (MRI) brain and bone scans- negative for any metastases • Positron emission tomography (PET) scan- hypermetabolic nodules in the lung and multiple suspicious nodes in the neck, chest, and abdomen, suggesting advanced stage IV lung cancer.
CONT’S.. TREATMENT • Initially treated with carboplatin, pemetrexed, and paclitaxel for a total of 4 cycles. She responded well to the treatment with a decrease in the size of pulmonary tumor nodules • Completed 8 cycles of maintenance pemetrexed, and on follow-up, a CT scan revealed the right upper lobe lung nodule to have increased in size from the previous 1 x 0.7 cm to 1.5 x 0.8 cm • At this time, she was started on nivolumab (3 mg/kg/dose). 6 months following commencement of nivolumab. The lung lesions remain unremarkable since then.
CONT’S.. • Her performance status was stable at ECOG-PS-0 over the 4 years of treatment • After being on treatment for almost 4 years, the patient developed a pruritic, hyperpigmented rash on the upper and lower extremities and trunk. • At this time, she received a treatment break from nivolumab while she was treated with steroids (1 mg/kg/day of prednisone) and hydroxyzine.
CONT’S.. • On the resolution of her rash, she was restarted on nivolumab. The patient presented to ER and was subsequently admitted for significant posterior epistaxis and melena along with a drop in her haemoglobin. A CT head scan was performed as part of the workup for severe posterior epistaxis, which showed a 10 mm enhancing lesion in the posterior left frontal lobe, suspicious for metastatic disease. MRI brain confirmed a 0.9 cm enhancing lesion at the posterior left frontal lobe
CONT’S.. • The patient showed resolution of lung lesions on CT and no disease progression on nivolumab for 3 and a half years. • However, the MRI brain scan showed a new solitary metastasis in the brain, which was treated with stereotactic radiosurgery
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