Mylene Freires Advanced Nurse Practitioner, Haematology Overview of Cancer Mylene Freires Advanced Nurse Practitioner, Haematology

Aim of the Presentation Review basic concepts of cancer Gain some understanding of the socio-economic impact of cancer

Order of Presentation: A. Global Cancer Statistics and in the UK B. Cancer Basic Concepts C. Grading, Risk Factors and Genetics D. Diagnosis and Staging E. Prognosis and Treatment

Why is Cancer everyone’s business? Personal reasons Professional reasons Socio-economic impact

A. Worldwide Cancer Statistics: In 2012, 14.1 million of new cases worldwide 8.2 million deaths worldwide 33% are linked with smoking; 6% alcohol drinking prevalent in Europe and America Higher in males then females

UK statistics: < X X Survivors in 10 years

UK statistics,2015 New cases 359,960 More males than females Deaths 163,444 Only 50% survive cancer for 10 years or more 42% of Cancers are preventable More males than females Incidence rates are highest in people aged 85 to 89

Most common cancers: Lung -1/5 of all cancer deaths Bowel Prostate Breast

Financial Impact to Economy: Loss of people from the labour force 50,000 deaths = £585 million loss and across their lifetime = £6.8 billion

Financial Impact to: Families and communities: Loss Caregivers Loss or Reduced Income =£570- £860/month Increased costs related to inpatient and outpatient attendances Loss of Vital volunteers £236 million/year

Cancer Survivors:

Cancer Survivors’ estimated contribution: 1.8 million survivors = £6.9 million contribution through paid employment Informal care = 258 million hours Volunteering = 52 million hours Domestic work = 1.5 billion hours

Financial Cost £16.7 billion Cancer Survivors’ social contribution is estimated at: £16.7 billion

B. Cancer Basics: What is Cancer?

Cell Cycle

Phases of cell cycle G1, S & G2 Known as the interphase Cells spend more time in interphase than mitosis At each phase there are check points, if conditions are right proteins determine whether enter into the next phase If conditions not right will stay in GO Phase ( resting phase)

G0 Known as the resting phase . The cell is not currently in it’s cycle. G1 Cell increases in size checkpoints occur prior to Synthesis Synthesis The cell replicates G2- The gap between synthesis and mitosis another checkpoint prior to mitosis

Mitosis ( Also known as cell division) Cell growth stops and cells divide into 2 daughter cells. Goes through 4 phases during this phase Prophase Metaphase Anaphase Telophase Cytokinesis

What is Cancer? Is a collection of related disease. A complex disease with variable presentation, development and outcome from one patient to another. It is a multi-step process- involving cellular metabolic and behavioural changes leading to untimely and excessive proliferation. Cumulative modifications in the genetic programmes that control cell proliferation, lifespans and the ability to escape the immune system.

Why cells become malignant?

Three Conditions In Cancer Transformation: cells should proceed to divide only when they receive appropriate signals when confronted by stressful or improper conditions for DNA replication, cells activate self-destruction programmes rather than allow DNA replication to proceed in conditions where genes may become damaged normal cells divide only a limited number of times

Genetic Drivers in Cancer: Proto-oncogenes- (KRAS) Proto-oncogenes are genes that normally helps cells grow. They help regulate cell growth. However, proto-genes can mutate or if there is a change in their dna sequence, they change they can become oncogenes. When this happens, this leads to unregulated cell division, a slower rate of cell differentiation and increased inhibition of cell death. Together, these features define cells that have become cancerous. Tumour suppressor genes act as braking signals during phase G1 of the cell cycle, to stop or slow the cell cycle before S phase. If tumor-suppressor genes are mutated, the normal brake mechanism will be disabled, resulting in uncontrolled growth, i.e. cancer. DNA repair genes code for proteins whose normal function is to correct errors that arise when cells duplicate their DNA prior to cell division. DNA repair genes are active throughout the cell cycle, particularly during G2 after DNA replication and before the chromosomes divide. Mutations in DNA repair genes can lead to a failure in repair, which in turn allows subsequent mutations to accumulate.

Tumour suppressor genes (TP53 and RB1)

DNA Repair Genes

Cells become cancerous due to the accumulation of defects, or mutations, in their DNA Certain inherited genetic defects (for example, BRCA1 and BRCA2 mutations) and infections can increase the risk of cancer. Environmental factors (for example, air , pollution , poor life style choices eg smoking alcohol can increase cancer

Sources of DNA Damage:

Cancer occurs when when certain cells in the body keep dividing without the ability to stop Feeds off the body ( contributes to weight loss) Carcinogenesis- or oncogenesis or tumorigenesis is the actual formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by a progression of changes at the cellular, genetic, and epigenetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thereby forming a malignant mass.

Types of Cancers: Haematological Malignancies Solid tumours Carcinoma adenocarcinoma basal cell carcinoma squamous cell carcinoma transitional cell carcinoma Sarcoma Melanoma Brain and Spinal Cord Tumours Other Tumours: germ cell tumours Leukaemias Lymphomas Multiple Myelomas Carcinoma from epithelial cells; adenocarcinoma from those producing fluids or mucus; basal cell; lower layer of the epidermis; squamous cell those that lie beneath the outer surface of the skin; transitional cell those that can get bigger and smaller i.e bladder, ureters, kidneys Sarcomas form from bone and soft tissues, including fat, muscles blood vessels Melanoma from melanocytes or melanin

C. Grading Tumours: Well-differentiated tumours Poorly differentiated or “undifferentiated” Assigned with numerical grade and is not the same as cancer staging Or Grade 1 Grade II Grade III

D. Cancer Staging: Refers to the location and extent of the tumour spread 4 Factors: Location of Primary tumour tumour size and extent Lymph node involvement Presence or absence of metastasis

TNM staging system N : number of nearby lymph nodes with cancer T : size and extent the main tumour N : number of nearby lymph nodes with cancer M : metastasized Numbers after each letter provides more details e.g: Primary tumour (T) TX: main tumour cannot be measured T0: main tumour cannot be found T1, T2 etc: refers to the size and/ or extent of main tumour

Regional Lymph Nodes: NX: cancer in lymph nodes cannot be measured N0: No cancer in nearby lymph nodes N1, N2, N3: Number and location of lymph nodes with cancer; Distant Metastasis: (M) MX: metastasis cannot be measured M0: cancer has not spread M1: Cancer has spread

Stage Meaning Stage 0 Stage I, II and III Stage IV Abnormal cells are present but not spread nearby tissue i.e CIS Cancer is present. The higher the number, the larger the cancer tumour and spread Cancer has spread to other parts

Other staging categories: In situ Localised Regional Distant Unknown Abnormal cells but have not spread Limited to the place where it started with no sign of spread Has spread to nearby lymph node, tissues or organs Has spread to distant parts of the body Not enough information

E. Prognosis in Cancer: “prediction about a patient’s future” Refers to the likelihood of response to treatment and survival

Factors affecting Prognosis of Cancer: The type of cancer and where it is in The stage of the cancer, which refers to the size and if it has spread The cancer’s grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about how quickly the cancer is likely to grow and spread. Certain traits of the cancer cells Age and fitness before cancer Response to treatment

F. Treatments for Cancer: Chemotherapy Surgery Radiation Therapy. Immunotherapy. Targeted Therapy. Hormone Therapy. Stem Cell Transplant. Precision Medicine

Thank you. Email: Mylene.Freires@bfwhospitals.nhs.uk

Resources: National Cancer Institute Cancer Research UK UK Statistics office www.ilcuk.org.uk Macmillan