Non-Small Cell Lung Cancer

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1 Non-Small Cell Lung Cancer John delcharco, MD (Statistics based on CVMC data ) Statistics Lung cancer is the leading cause of cancer deaths in the United States. The American Cancer Society estimates 228,190 new cases of lung cancer (118,080 in men and 110,110 in women) in the United Stated in Deaths from lung cancer are estimated to be 159,480 (87,260 in men and 72,220 in women). The rate of lung cancer has been dropping for the past two decades for men and has just begun to drop for women. Catawba Valley Medical Center (CVMC) newly diagnosed lung cancer rates from : CVMC- New Lung Cancer by Year % % % % % Total % Lung cancer is divided into two major categories: small cell and non-small cell lung cancers. Non-small cell lung cancers (NSCLC) are slower growing and less sensitive to chemotherapy and radiation therapy than small cell lung cancers. Non-small cell lung cancers (NSCLC) are the focus of this in-depth study. Small Cell & Non-Small Cell Lung Cancer Categories CVMC Description Count % Small cell Lung Cancer % Non-Small cell Lung % Total % Non-small cell lung cancers comprise 85-90% of all lung cancers and the three main types are adenocarcinomas, squamous cell carcinomas, and large cell carcinomas. About 40% of all lung cancers are adenocarcinomas. Adenocarcinomas occur in smokers and non-smokers and are the most common lung cancers found in nonsmokers. They are more common in women and in younger people than other lung cancers. Adenocarcinomas tend to occur in the peripheral areas of the lungs and are usually slower growing than other types of lung cancer. It is the lung cancer most likely to be found before it has metastasized to other parts of the body. Squamous cell (epidermoid) carcinomas (25-30%) occur in the flat cells that line the airway. They tend to occur centrally near the bronchus. They are usually linked to a history of smoking. Large cell (undifferentiated) carcinomas (10-15%) occur in any part of the lung. They tend to be the fastest growing NSCLC and spread quickly making treatment more difficult. There are other rare types of NSCLC, such as adenosquamous carcinomas and sarcomatoid carcinomas.

2 NSCLC Histology CVMC # Description Count % /3 Adenocarcinoma % 8070/3-8073/3 Squamous Cell Carcinoma % 8046/3 Non-Small cell carcinoma, NOS 51 12% 8012/3-8013/3 Large Cell Carcinoma 21 5% 8010/3 Carcinoma, NOS 14 3% 8250/3 Bronchiolo-alveolar Adenocarcinoma 6 1% 8252/3-8254/3 Bronchiolo-alveolar Carcinoma 4 1% All other Other 20 5% Total %

3 Risk Factors Smoking is attributed to causing at least 80% of all lung cancers. Smoking pipes and cigars are almost as risky as smoking cigarettes. Second hand smoke is also dangerous. A nonsmoker who lives with a smoker has a 20-30% higher risk. Radon gas is considered to be the second leading cause of lung cancer in the United States. This odorless gas occurs from the breakdown of uranium in soil and rocks. Houses built on uranium rich soil can develop high concentrations of radon. Asbestos is a well-known work related substance that can cause lung cancer, but arsenic, uranium and certain petroleum products are other industrial carcinogens. Workers who deal with certain types of insulation, brake repair, or coke ovens are also at increased risk. When occupational exposure is combined with smoking, the risk of developing lung cancer is sharply increased. Some other risk factors for lung cancer include: Air pollution Arsenic in drinking water Radiation to the lungs Personal or family history Beta carotene supplements when taken by smokers Another possible risk factor still being studied is marijuana use. Early Detection Early NSCLC generally do not cause symptoms. By the time that a patient presents with symptoms, the lung cancer is usually advanced (Stage III/IV) disease. Symptoms of lung cancer include: Persistent cough Constant chest pain that may increase with coughing, laughing, or deep breathing Hemoptysis Repeated bouts of pneumonia or bronchitis Dyspnea, wheezing or hoarseness Weight loss or anorexia Fatigue Fever of unknown origin When lung cancer spreads beyond the lung, other symptoms may be: Bone pain Neurologic changes Jaundice Palpable lymph nodes Skin nodules Early diagnosis and treatment offer the best chance of survival for patients with NSCLC. In 2012, the National Comprehensive Cancer Network established guidelines for the lung cancer screening using low dose spiral CAT scan for individuals at high risk. High risk is defined as individuals between the ages of who currently smoke or quit smoking within the past 15 years and have 30-year pack history. In November 2013, CVMC, started a lung cancer screening program.

4 Diagnosis Diagnostic work-up may include: Chest x-rays CT of the chest with or without contrast CT scan of the brain MRI of the chest and/or brain Sputum collection Radionuclide scanning PET (Positive Emission Tomography) PET/CT combination Bone scan Endobronchial or endoscopic esophageal ultrasound Biopsy obtained by: o Needle aspiration o Thoracotomy o Thoracentesis o Bronchoscopy o Mediastinoscopy

5 Staging All NSCLCs are staged according to the American Joint Committee on Cancer (AJCC) TNM System of Cancer Staging. Staging may include both a clinical and a pathologic staging. Clinical staging is based on physical exam, biopsies and imaging studies. If surgery is performed, a surgeon may give a pathologic staging which includes criteria for a clinical staging plus what is found during the surgery. Since many patients do not have surgery, they will only have clinical staging. The National Cancer Database (NCDB) 2010 record (last reported data) showed that more than over 60% of NSCLCs were found to be in advanced stages (III or IV). Stage Percentage 0 0.4% I 24.8% II 10% III 19.9% IV 40.2% OC 0.1% Unknown 4.7% Statistics for CVMC confirm that trend as seen in chart below. Stage III and IV NSCLC make up 67% of newly diagnosed cases at CVMC from New Non-small Cell Lung Cancer by AJCC Best Stage Group CVMC Stage Grp Count % 1A % 1B % 2A % 2B % % 3A % 3B % % % OCCULT % Total % New Total NSCLC by Combined Stage CVMC Stage 1 99 stage 2 34 Stage 3 99 Stage Unknown 2 Occult 1 Total 414

6 According to the American Cancer Society five year survival rate by stage is: Stage Percentage IA 49% IB 45% IIA 30% IIB 31% IIIA 14% IIIB 5% IV 1% Catawba Valley Medical Center five year survival rate by stage is displayed:

7 Treatment Treatment depends on the stage of the cancer and the condition of the patient. Standard treatment options include surgery, radiation therapy, laser therapy, photodynamic therapy, chemotherapy and biotherapy. Patients that have a Stage I or II NSCLC that is resectable have the best prognosis; however, only a small percentage of the patients diagnosed and/or treated at CVMC with NSCLC have early resectable tumors. Curative surgeries include pneumonectomy, lobectomy, and segmentectomy or wedge resection. Surgery may be performed to lessen symptoms or to place central line catheters for treatment. Radiation therapy can cure a small minority and provide palliation in the majority of patients. External beam radiation is the most common type of radiation used. Intensity Modulated Radiation Therapy (IMRT) is an advance 3D treatment used at Catawba Valley Medical Center. As well as better defining the treatment area, IMRT also can deliver different amounts of radiation to different areas in the treatment field. Rarely, internal radiation (brachytherapy) is used to shrink tumors in the airways that are causing symptoms. Other local treatments include photodynamic therapy, laser therapy, radiofrequency ablation, and stent placement. Photodynamic therapy is used for very early stage lung cancer or to open blocked airways. A light-activated drug is injected into the veins. After a few days, a bronchoscope with a special laser light is used to treat the tumor. Laser therapy is used for the same reasons as photodynamic therapy. A laser at the end of a bronchoscope aims a beam to destroy cancer cells. For radiofrequency ablation, a probe is inserted using a CAT scan. Once the probe is in place, an electric current is discharged through the probe. This heats and destroys the cells. This is usually only used for early stage tumors, peripheral tumors, especially for patients who can t tolerate or don t want surgery. Stents are used to open narrowed airways. Chemotherapy offers modest improvement in median survival rate, but the overall survival rate remains poor. According to the American Cancer Society, the most common chemotherapy agents for NSCLC are: Cisplatin Carboplatin Paclitaxel (Taxol ) Albumin-bound paclitaxel (nab-paclitaxel, Abraxane ) Docetaxel (Taxotere ) Gemcitabine (Gemzar ) Vinorelbine (Navelbine ) Irinotecan (Camptosar ) Etoposide (VP-16 ) Vinblastine Pemetrexed (Alimta ) From research into how cancers grow, targeted therapies have been developed. Targeted therapies are a relatively new treatment for NSCLC and generally have fewer side effects than chemotherapy. Bevacizumab (Avastin ) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) which stimulates blood vessel growth. Normal cells, as well as some cancer cells, produce VEGF when they experience an inadequate oxygen supply. By slowing the growth of new blood vessels, tumors have a decrease blood supply, oxygen levels and nutrients, which slows tumor growth. Epidermal growth factor receptor (EGFR) is a protein found on the outside of cells. It helps the

8 cells divide and grow. Some non-small cell lung cancers have too many EGFRs which makes it grow faster. Erlotinib (Tarceva ) blocks the EGFR from signaling the cell to grow. Cetuximab (Erbitux ) is a monoclonal antibody that targets EGFR. Numerous clinical trials for treatment of NSCLC are underway. Not all patients are candidates for clinical trials. Information about clinical trials is available at cancer.gov. The American Cancer Society offers a clinical trial matching service at

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