Lung Cancer By, Nazneen Chougle Neha Bhatkal Nilekha Kalyankar Nirali Bavaria Namrata Gaokar

Contents Introduction Signs and Symptoms Pathophysiology Statistics Diagnosis Treatment Recent Clinical Trials Palliative Care and Case Study Ethical Considerations

Tumors Malignant tumors Benign tumors They are cancer. Can invade and damage tissues and organs near the tumor The spread of cancer is Called metastasis Benign tumors They are not cancer. Do not spread to other parts of the body and are not a threat to life.

Lung Cancer: Defined Uncontrolled growth of malignant cells in one or both lungs and tracheo-bronchial tree. A result of repeated carcinogenic irritation causing increased rates of cell replication. Proliferation of abnormal cells leads to hyperplasia, dysplasia or carcinoma in situ. 90%-95% of cancers of the lung arise from the epithelial cells, the cells lining the larger and smaller airways

Two Types Of Lung Cancer Cells Non Small Cell Lung Cancer (NSCLC) Most common type Grows and spreads more slowly than small cell lung cancer Three main types Adenocarcinoma Squamous Cell Carcinoma (epidermoid carcinoma) Large Cell Carcinoma Small Cell Lung Cancer (SCLC) Called oat cell cancer Less common Grows more quickly Spread to other organs in the body

Where D oes it Come From? Smoking Passive smoking Radon gas Familial predisposition Lung diseases Prior history of lung cancer Air pollution

Signs and symptoms No symptoms in up to 25% of people Symptoms related to the cancer cough dyspnea hemoptysis recurrent infections chest pain Symptoms related to metastasis Paraneoplastic symptoms. Nonspecific symptoms.

Deaths Due to Lung Cancer

DIAGNOSIS H ISTOR Y AN D PH YSICAL E XAMINATION Cyanosis Chest x- ray CT (computerized tomography, computerized axial tomography, or CAT) scans L OW- DOSE HELICAL CT SCAN (or spiral CT scan) MAGNETIC RESONANCE IMAGING(MRI). P OSITRON EMISSION TOMOGRAPHY (PET) BLOOD TESTS

DIAGNOSIS BONE SCANS: These are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. SPUTUM CYTOLOGY : If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis

DIAGNOSIS BRONCHOSCOPY: Examination of the airways by bronchoscopy (visualizing the airways through a thin, fiberoptic probe inserted through the nose or mouth) may reveal areas of tumor that can be sampled (biopsied) for diagnosis by a pathologist. NEEDLE BIOPSY: Fine needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs.

DIAGNOSIS DIAGNOSIS T HORACENTESIS: Aspiration of a sample of this fluid with a thin needle (thoracentesis) may reveal the cancer cells and establish the diagnosis. MAJOR SURGICAL PROCEDURES Mediastinoscopy Thoracotomy

Recent Advances Biomarkers Fluorescent in-situ hybridization techniques (FISH) Super Dimension(R)/Bronchus System (SDBS) Computer-aided detection (CAD) Breath tests

Contd…. Auto fluorescence bronchoscopy (AFB) Endobronchial ultrasound (EBUS) Coherence tomography (OCT)

CHEMOTHERAPY Used for both NSCLC and SCLC Used in combination with radiation therapy and surgical therapy. Platinum based drugs most effective- Cisplatin May be given as pills, as an intravenous infusion, or as a combination of the two. Second-line chemotherapy is used to treat recurrent cancers that have previously been treated with chemotherapy. Side effects- Nausea, Vomiting, weight loss, hair loss, mouth sores, etc

RADIATION THERAPY Curative therapy, palliative therapy or as adjuvant therapy in combination with surgery or chemotherapy. Used for both NSCLC and SCLC Uses high energy X-rays to kill dividing cells. Brachytherapy Shrinks a tumor or limits its growth when given as a sole therapy Simulation is necessary prior to treatment. Side effects- fatigue, lack of energy, reduced WBC count and blood platelet levels, irritation of skin, nausea , Vomiting, diarrhoea.

SURGERY Generally performed for limited-stage (stage I or sometimes stage II) NSCLC. Surgery may not be possible if the cancer is too close to the trachea. Depends upon the size and location of the tumor. Could require lobectomy (removal of one lobe) pneumonectomy (removal of an entire lung) or lymphadenectomy (removal of lymph nodes). If a recurrent cancer is confined to one site in the lung. Side effects-difficulty breathing, shortness of breath, pain, and weakness.

PHARMACOTHERAPY Erlotinib (Tarceva), is used in patients with NSCLC who are no longer responding to chemotherapy. Also called as “The Targeted Drug” because it targets a protein called the Epidermal Growth Factor Receptor (EGFR) that is important in promoting the division of cells. Iressa (Gefitinib) Antiangiogenesis drugs- Bevacizumab (Avastin) Vadimezan – Disrupts Blood Vessels within tumors. Bisphosphonates. ARQ 197 Tragedy Exubera –inhaled Insulin ,manufactured by Pfizer had promised of letting diabetics avoid needle sticks but actually increased the cases of lung cancer in diabetic patients. Drug has been withdrawn.

NON SMALL CELLED LUNG CANCER SMALL CELLED LUNG CANCER OTHER IMPORTANT DRUGS NON SMALL CELLED LUNG CANCER SMALL CELLED LUNG CANCER Alimta Erlotinib Docetaxel Etoposide Gemzar Hyacamtin Navelbine Tarceva Onxol Topotecan Paclitaxel VePesid Photofrin Taxol Taxotere Vinorelbine Gemcitabine Pemetrexed Porfimer Gefitinib

Other Newer Therapies PHOTODYNAMIC THERAPY (PDT) RA DIO FREQUENCY ABLATI O N CHINESE MEDICINES Ligustrum lucidim Ait. (Tree Pivet), Astragalus membranaceous Suppress tumor angiogenesis, promote dormancy of cancerous cells, induce re-differentiation of cancer cell, directly kill cancerous cells， and it is effective against recurrence and metastases of cancer. CRYOSURGERY

IMMUNOTHERAPIES MONOCLONAL ANTIBODIES “ Humanized” antibodies- Trastuzumab ANTIGEN SPECIFIC VACCINES Incorporating cytokines into anti-tumor vaccines Biomarkers Radioactive agents By cutting off a key gene,14-3-3zeta, lung cancer tumour cells are left 'homeless‘ and they can't survive on their own.

Clinical trials for lung cancer A Study to Diagnose Lung Cancer by Sputum Cytology. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-Small Cell Lung Cancer. INS316 in Diagnosing Lung Cancer in Patients With Untreated Lung Cancer Prevention of Tumour Spread Due to Lung Cancer Surgery. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer.

Clinical trials for lung cancer- ongoing Biomarkers for Early Detection of Lung Cancer in Patients With Lung Cancer, Participants at High-Risk for Developing Lung Cancer, or Healthy Volunteers A Clinical Trial to Validate Molecular Targets of Vorinostat in Patients With Stage I-III Non-Small Cell Lung Cancer DNA Analysis in Predicting Lung Cancer Risk Phase II Study of Dichloroacetate (DCA) in Patients With Previously Treated Metastatic Breast or NSCL Cancer Sputum Cytology in Screening Heavy Smokers For Lung Cancer

Recent research Tumor Growth Pattern May Predict Survival in Non-Small Cell Lung Cancer Newer techniques to combact with non-small cell lung cancer and small cell lung cancer. Hormone with anti cancer effects.

Quality of life Means how lung cancer survivors feel about different aspects of life, including physical health, emotional health, and ability to carry out daily activities. opinions about their quality of life, as well as the factors that affect their quality of life. Helps to develop new services for lung cancer survivors. Behavioral Questionnaires or Telephonic Interviews are conducted.

Palliative Care in Lung Cancer Symptom Palliative Recommendations 1) Pain Mild : Acetaminophen or NSAIDs Severe : Opioids 2) Dyspnea Oxygen, Bronchodilators, Corticosteroids, Antibiotics, Opioids 3) Cough Non opioid cough suppressants, Bronchodilators, Corticosteroids, Opioids 4) Bone Metastases External Radiation Therapy + Systemic Corticosteroids (Prednisone 20 to 40 mg) 5) Brain Metastases Dexamethasone (20mg) for 4 weeks 6) Spinal cord Compression High Dose Steroids + Radiation Therapy Adjunct Therapy : Dexamethasone (60mg)

Palliative Care Centers Fox Phase Cancer Centre, Philadelphia, USA Barbara Ann Karmanos Cancer Hospice, Southfield, USA John Taylor Hospice, Birmingham, England The Prince of Wales Hospice, Yorkshire, England St. Luke’s Hospice, Plymouth, England Primrose Hospice, Worcestershire, England St. Francis Hospice, Ireland Royal Perth Hospital, Australia Shanti Avedna Ashram Chittaranjan National Cancer Institute 11) Christian Medical Association of India 12) Cipla Foundation's Cancer Palliative Care Centre

Ethical Considerations Should terminally ill cancer patients be allowed to try new therapies with no clinical trials? Should they worry about the side effects? Personal Autonomy v/s Justice. Imposing the truth on an unprepared patient. Cultural Sensitivity and Cultural Competence. Special aspects of truth telling in pediatric and geriatric oncology. Euthanasia and Physician-assisted Suicide

Lung Cancer Awareness November is Lung Cancer Awareness Month. The colour of lung cancer awareness is Pearl White. ‘Can Support’ organized walkathon called “Walk for Life” on 7th Feb 2010 in New Delhi to create awareness about Lung Cancer.

Case Study In March 2004, 46 yr old non-smoker, Caucasian female, presented with flu-like symptoms, persistent cough and constant fatigue. Biopsy and CT scan revealed NSCL cancer in the right lung. Surgery was scheduled a month later to remove the nodular mass and the entire right middle lobe of the right lung. In May 2005, additional nodules appeared in the mediastinal area and a biopsy and mediastinoscopy revealed mucin- producing adenocarcinoma in stage II B. PET scan done in May 2006 revealed liver and right pleural space metastasis. The patient received chemoradiation therapy consisting of weekly Carboplatin (Platinol) plus Paclitaxol (Taxol), concurrent with radiation therapy. Experimental Phase I/II clinical trial with oral Tarceva (Erlotinib) and oral Vorino stat. Brachytherapy to the trachea.

Some Interesting Facts Most common form of cancer worldwide. 1.2 million new cases of lung cancer worldwide every year. Responsible for 17.8% of all cancer deaths annually. Kills about 9,00,000 men and 3,30,000 women annually In Men smoking causes more than 80% of lung cancer cases. In Women it causes 45% of all lung cancer cases.

Summary Lung cancer is the leading cancer-related cause of death. It has become the subject of a great amount of research. The best way to prevent it is to quit (or never start) smoking. Treatment depends on the cancer's specific cell type, how far it has spread and patient's performance status. It also depends on the stage, or how advanced it is. Treatment includes chemotherapy, radiation and surgery. In recent years, various molecular targeted therapies have been developed as treatments.

REFERENCES www.cancer.gov/cancertopics/types/lung www.daviddarling.info/encyclopedia/L/lung_cancer_treatment.html www.merck.com/mmhe/sec04/ch057/ch057a.html www.clinicaltrials.gov Medscape,clin lung cancer 2009-10, By, Everrete and E.Vokes PNAS journal Volume 100, July 8th, number 14

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