15-Cancer epidemiology and management 2019 (1).pdf

Neoplasia Learning objectives Epidemiology – Management 1. Understand global and UK incidence, prevalence and trends of common cancers Gillian Hall 2. Understand the influence of regional and socioeconomic factors on common cancers 3. Understand global and UK incidence, prevalence and trends of oral...

Neoplasia Learning objectives Epidemiology – Management 1. Understand global and UK incidence, prevalence and trends of common cancers Gillian Hall 2. Understand the influence of regional and socioeconomic factors on common cancers 3. Understand global and UK incidence, prevalence and trends of oral and head & neck cancer 4. Understand the application of the common cancer treatments and their biological mechanisms Cancer risk factors Cancer Hundreds of types Define by site: oral, lung, bowel, breast……. Define by histology: carcinoma, sarcoma, melanoma, lymphoma………. 1/4 UK deaths some income tages Age > 55 yrs Obesity PTCH1 mt Genes PTEN mt BRCA1,2 mt & breast cancer Cancer incidence UK 2015 Older ages Lifestyle Environment Oncogenic viruses e.g. HPV & cervical cancer Cancer incidence UK 2015 Kinde breastsprostatelong to retastasize Kare - 1 UK Cancer incidence by age 2012-2014 Changes in UK male cancer incidence rates (2003-2005 vs 2013-2015) Changes in UK female cancer incidence rates (2003-2005 vs 2013-2015) Head and Neck Cancer incidence 1993-2015 English Cancer incidence by deprivation 2007-2011 (all cancers excluding non-melanoma skin) Oxford Cancer Intelligence Unit 2010 2 Worldwide cancer incidence Global incidence of lip and oral cancer 2012 Epstein-Barr Virus Cancer a co lymphomaborcit causing Human Herpesvirus-8 R Burkitt lymphoma Nasopharyngeal carcinoma Kaposi sarcoma 3 Biopsy and diagnosis Cancer management piece of > - head tissue Incisional biopsy: Histopathological diagnosis Fine needle aspiration: Cytological diagnosis Many steps Big team Patients first and foremost + Imaging vital role in cancer care ↳ Guided biopsy e.g ultrasound guided thyroid fine needle aspirations biopsy good for for Softlisse MRI -> soff Tissue where ? Response: Growth or shrinkage Follow-up: Re-growth and spread good > - CT Lamalgam effects Screening e.g. mammography Staging: Site, size, and spread not ↳ sproach following radiotherapy -bigger ? > - smaller : PET d Op picks that suls we hig one his one metaboli active Orthopantomagram More US red wire abolic ↳mar superticaly localedums bumps B half sided O 4 Surgery Solid tumours Surgically remove entirely Is the patient well enough? Is the surgery safe? Think about: carotid artery, spinal cord etc….. Radiotherapy Treatment of disease using radiation Use of ionising radiation to kill tumour cells Ionising radiation Most radiation energy initially absorbed by water Reactive oxygen species generated DNA damaged – with the intention of sending targeted cells down the apoptosis pathway Rely on apoptotic mechanisms working and not mutated Brachytherapy: Radioactive sources placed within body e.g. Cs-137 for cervical cancer External beam radiotherapy Ionising radiation applied from an external source: Usually x-rays and gamma rays e.g oral cancer Proton beam therapy: High precision Radical radiotherapy: Given to cure e.g. small cancers of larynx Neoadjuvant radiotherapy: Improve local control pre-operatively e.g. rectal cancer Radionuclides: Certain radioisotopes are taken up by a particular tumour cell type e.g. Iodine-131 for thyroid cancer Adjuvant radiotherapy: Improve local control after complete surgical resection (belts and braces / building fences) Post-operative radiotherapy: Treat residual disease Palliative radiotherapy: Enhance quality of life but not cure e.g. painful bone metastases 5 Early side effects of radiotherapy Anorexia, malaise Damage to highly proliferating tissue – Mouth and GI: Mucositis, ulcers. – Hair follicle: Alopecia – Bone marrow: Myelosuppression Late side effects of radiotherapy Fibrosis, bowel stenosis, infertility Xerostomia, endarteritis obliterans, osteonecrosis Second malignancies Curative chemotherapy: e.g. lymphoma. Prophylactic chemotherapy: e.g. tamoxifen for in situ breast cancer (dysplasia) Neoadjuvant chemotherapy: Primary treatment before surgical management e.g. osteosarcoma Adjuvant chemotherapy: Follows surgery e.g. treatment of micro metastases in breast cancer Palliative chemotherapy: Enhance quality of life and/or prolong it but not to cure Chemotherapy Use of chemical substances to treat disease Usually for disseminated / systemic disease In cancer this includes: Cytotoxic drugs Hormonal therapies Biologicals or targeted therapies Cytotoxic chemotherapy Systemically administered Many different modes of action depending on drugs used Some damage DNA promoting apoptosis and necrosis like radiation treatment Tumours develop resistance to single agents so drugs combined Not cancer specific and damage normal tissue. Chemoradiotherapy Narrow window between therapeutic and toxic doses Cytotoxic chemotherapy DNA damaging agents e.g. cisplatin Platinum compound Causes DNA cross links Role in head and neck cancer Cytotoxic chemotherapy Anti-tubulin agents e.g. vincristine Binds tubulin and inhibits microtubule formation in mitosis Treatment of lymphoma 6 Cytotoxic chemotherapy Side effects of cytotoxic chemotherapy Antimetabolites: Malaise, fatigue, vomiting Interfere with normal synthesis of nucleic acids 5-fluorouracil blocks synthesis of thymine Myelosupression, Mucositis, Alopecia Organ toxicity DNA repair inhibitors Infertility Inhibit topoisomerase II DNA breaks caused e.g. doxorubicin Hormonal chemotherapy Some cancers hormone sensitive. Tamoxifen binds and blocks oestrogen receptor – slows / stops growth of breast cancer Monoclonal antibodies Cetuximab: Anti- EGFR Used with radiotherapy to treat advanced head and neck cancers New developments Oncolytic viruses T-VEC: Modified HSV 1 Engineer it to be trophic to tumour cells Replicates within tumour cells Lysis and death of cell Induction of immune response Further spread of virus particles FDA approved for melanoma New developments Anti PDL1 Tumour cells frequently come into contact with CD8 positive T cells that recognise them as “abnormal” Tumour cells may express PDL1 on their surface which interacts with a receptor on the T cell (PD-1), essentially deactivating the T cell and preventing an immune response By blocking the PDL1 (or PD-1) receptor, we can terminate this ability to send a switch off message to the T cell. Cancer management Destroy every cancer cell Surgery, radiotherapy, chemotherapy Palliative care Multi-disciplinary teams (MDT) Core Head and Neck MDT Members Surgeons: ENT, Maxillofacial, plastics Oncologists Pathologists Radiologists Dentists Clinical nurse specialists Speech and language therapists Senior nursing staff from the head and neck ward Palliative care specialists Dieticians Team secretary , Data manager, MDT co-ordinator 7