Introduction to Cancer: Site-Specific Malignancies PDF

Introduction to Cancer RPB40702 Cancer Treatment & Chemotherapy Presentated by Group Borcelle Site Specific Malignancy Course Learning Outcome Distinguish common therapeutic agents used in the treatment of cancer and their mechanism of actions, side effects, contrain...

Introduction to Cancer RPB40702 Cancer Treatment & Chemotherapy Presentated by Group Borcelle Site Specific Malignancy Course Learning Outcome Distinguish common therapeutic agents used in the treatment of cancer and their mechanism of actions, side effects, contraindications, adverse drug effects and drug-drug interactions (C4, PLO1) Recommend appropriate drugs for the treatment of selected gastrointestinal and respiratory disorders (C5, PLO1) Demonstrate good teamwork, communication, critical thinking and problem solving skills in group work (A3, PLO5, PLO6) Topic Outline 1.8.1 Hematologic malignancies 1.8.2 Head and neck cancer 1.8.3 Breast cancer 1.8.4 Lung cancer 1.8.5 Gastrointestinal cancer 1.8.6 Endocrine Associated cancer 1.8.7 Bone and soft tissue sarcomas 1.8.8 Urogenital malignancies Topic Outline 01 Introduction 02 Pathophysiology 03 Diagnostic criteria 04 Management RECAP! It originates from epithelial cells of the body It mixes one or different type of cancers It occurs in supportive and connective tissues It develops in the glands or nodes of the lymphatic system It associated with the overproduction of immature WBCs. It originates in the plasma cells of bone marrow 1.8.1 HEMATOLOGIC MALIGNANCIES Introduction For most (solid) cancers, the primary site of the most important factor for the prognosis and the choice of treatment For other cancers, especially haematological malignancies, the morphological classification is the most important factor Introduction White blood cells White blood cells, also known as leukocytes, Red blood cells Red blood cells, also known as erythrocytes,  Platelets Platelets, also known as thrombocytes Cellular Hierarchy & Differentiation Stem Cells undifferentiated cells with the unique ability to develop into specialized cell types in body. Hematopoietic Stem Cells (HSCs): responsible for producing all the different cells in the blood (red blood cells, white blood cells, and platelets). Cellular Hierarchy & Differentiation -HSC is multipotent ability of a single cell to differentiate into several cell types within a particular lineage or closely related family of cells. Known as progenitor cell Definition of hematologic cancer Cancer that begins in blood-forming tissue, such as the bone marrow, or in the cells of the immune system. Examples of hematologic cancer are leukemia, lymphoma, and multiple myeloma. Also called blood cancer. Reference: National Cancer Institute History of hematologic cancer In 1832, Thomas Hodgkin described the first hematologic malignancy. The first type of lymphoma was described in “On Some Morbid Appearances of the Absorbent Glands and Spleen,” a paper published in 1832 Types of hematologic cancer Leukemia Lymphoma Myeloma Pathophysiology Pathophysiology Pathophysiology Pathophysiology  Criteria for diagnosis Clinical features Microscopy Large cells / small cells Specific characteristics (colour, amount of cytoplasm, type of cell nucleus, etc) Specific tests for proteins in the cytoplasm/cell nucleus/on the surfac (immunohistochemistry) Immunophenotyping Cytogenetics  Diagnostic Aim Aim: To determine the cell type and ‘the normal counterpart’ To determine subtypes which are relevant for the prognosis and/or the treatment 1. Clinical diagnosis breast cancer melanoma Burkitt lymphoma 2. Microscopy Small, mature cells with little Large cells (cytoplasm ++), cytoplasm, no mitoses (CLL) prominent nucleoli, mitoses (DLBCL) 3. Immunohistochemistry Expression of the estrogen receptor (ER) by using an immunostain for ER. The immunostain binds to the ER protein in the nucleus of the cancer cells and is detected by a positive brown colour 3. Immunohistochemistry Expression of HER2 by using an immunostain for HER2. The immunostain binds to the HER2 protein on the surface of the cancer cells and is detected by a positive brown colour 4. Immunophenotyping Technique for the detection of proteins in the cell membrane of cancer cells –Tissue –Blood –Bone marrow If a certain protein is absent of present this gives an indication for the type of cell 4. Immunophenotyping 5. Cytogenetics & molecular diagnostics Most cancer cells have ‘errors’ in the DNA (cytogenetic aberrations) With cytogenetics & molecular diagnostics these aberrations can be detected Many aberrations are not clinically relevant, but others are, because specific drugs can target specific cytogenetic aberrations, e.g. imatinib for BCR-ABL+ chronic myeloid leukaemia (‘targeted therapy’) Often, aberrations can be detected with different techniques 5. Cytogenetics & molecular diagnostics Cell nucleus Protein Gene Chromosome 5. Cytogenetics: karyotyping Photo of the chromosomes Each (normal) cell has 46 chromosomes In cancer cells a (part of a) chromosome can be missing, duplicated or displaced 5. Karyotyping: example Patient with MDS A part the long arm (q) of chromosome 5 is missing (=deletion) Diagnosis: MDS with 5q- Morphology code: 9986 5. Aberrations visible with karyotyping Deletion→ MDS with 5q- = M9986 Translocation → t(9;22) in CML =M9875 Inversion → AML with inv(3) = M9869 Trisomy (3 chromosomes in stead of 2) → Down syndrome (trisomy 21) Monosomy (1 chromosome in stead of 2) Hypodiploidy (46 chromosomes) → hyperdiploid ALL = M9815 5. Cytogenetics: Fluorescence in situ hybridisation (FISH) A fragment of RNA (‘probe’) is labelled with a fluorescent dye The probe binds to specific parts of the DNA (a gene or a larger part of the DNA) If the probe binds to a gene or part of DNA you see a fluorescent dot 5. FISH: example In CML there is a translocation of chromosomes 9 and 22 = t(9;22) Chromosome 9 is labelled red and chromosome 22 green. The normal situation is that you see 2 pairs of dots of the same colour (4 dots in total of each colour). If there is a combination red/green, the translocation is present. 5. Molecular diagnostics If a gene (or combination of genes = ‘fusion genes’) codes for a specific protein. The fusion gene in CML produces the protein BCR-ABL. The presence of the fusion gene BCR-ABL can be measured by detecting BCR-ABL RNA in the blood. Rules for classification Classify to the most specific (WHO) diagnosis Use all information from the different diagnostics Take into account that indolent haematological malignancies can transform to aggressive haematological malignancies For lymphoid malignancies the site of the tumour (lymph node, bone marrow) can also give an indication for the tumour type Principle of treatment  Take Home Massage Most blood cancers start in bone marrow, cancers affect the production and function of blood cells. Stem cells in bone marrow mature and develop into three types of blood cells: red blood cells, white blood cells, or platelets. In most blood cancers, the normal blood cell development process is interrupted by uncontrolled growth of an abnormal type of blood cell. These abnormal blood cells, or cancerous cells, prevent blood from performing many of its functions, like fighting off infections or preventing serious bleeding.  SOLID CANCER -BREAST CANCER -LUNG CANCER Topic Outline 01 Introduction 02 Pathophysiology 03 Diagnostic criteria 04 Management Incidence, Mortality and Prevalence by cancer site Reference: Malaysia - Global Cancer Observatory Reference: Malaysia - Global Cancer Observatory Reference: Malaysia - Global Cancer Observatory Reference: Malaysia - Global Cancer Observatory Reference: Malaysia - Global Cancer Observatory Pathophysiology BREAST CANCER  Breast cancer Pathophysiology: Hormonal, genetic (e.g., BRCA mutations), and environmental factors play roles. Triple assessment which consists of clinical assessment, imaging [ultrasound (US) and/or mammography] and pathology (histology and/or cytology) is an established method for the diagnosis Breast cancers are also classified by certain types of proteins or genes each cancer might make. estrogen receptors and progesterone receptors HER2 gene or protein Breast cancer can occur in both men and women, but it is more common in women.  Breast cancer Based on the consensus of CPG DG, the following conditions warrant early referral as early as possible (within two weeks) to breast clinic for further evaluation: women aged >35 years with signs and symptoms* high risk group with signs and symptoms* patients with clinical signs and symptoms of malignancy  Breast cancer General signs and symptoms: palpable mass breast pain nipple discharge  Breast cancer Signs of malignancy: hard and skin axillary fixed mass changes mass blood- image- asymmetric stained detected thickening/ nipple suspicious nodularity discharge lesion Breast Skin Changes Self Breast Examination BREAST CANCER  Lung cancer Pathophysiology: Smoking is a primary risk; there are also genetic mutations like EGFR. Diagnostics: Chest X-ray, CT scans, bronchoscopy, and biopsy. Lung cancers usually are grouped into two main types small cell lung cancer (SCLC) non-small cell lung cancer (NSCLC) Including adenocarcinoma and squamous cell carcinoma COPD: The Soil of Lung Cancer CASE STUDY 1. Risk factor of Oropharyngeal cancer 2. Suitability of regimen? Anti emetic? Adjunct treatment? 3.main treatment? Radiation? Chemotherapy? Need antiemetic? Potential side effect 4. Supportive care? Local guidelines 1. MINISTY OF HEALTH SYSTEMIC THERAPY PROTOCOL 2017 2. MANAGEMENT OF BREAST CANCER (3RD EDITION) 2019 3. MANAGEMENT OF CERVICAL CANCER (2ND EDITION) 2015 4. MANAGEMENT OF NASOPHARYNGEAL CARCINOMA 2016 5. MANAGEMENT OF COLORECTAL CARCINOMA 2017 6. MANAGEMENT OF CANCER PAIN 2010 7. CANCER DRUG COUNSELLING A GUIDE FOR PHARMACISTS 2016 International guidelines International guidelines Thank you!