Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Principles of Cancer Care Introduction Overall cancer incidence rising Some cancers have reduced incidence breast, colon, lung, prostate,lymphoma cervix, stomach, endometrial Second highest cause of mortality Principles of Cancer Care Terminology Neoplasia - new growth malignant - uncontrolled growth and dissemination Hyperplasia - increased cell number Metaplasia - mature cell type replacement Dysplasia - altered epithelial cell size, shape and orientation. CIS most severe form Principles of Cancer Care Causes of Neoplasia Immunodefficiency - transplant tumours, Kaposi Familial - Breast cancer, MEN, Lynch, FAP, Physical carcinogenesis foreign body - asbestos ionizing radiation Chemical carcinogenesis Viruses Biology of Cancer Clonality Most tumours arise from a single altered cell Most transformed cells die or are destroyed Surviving cell heritability escape from normal control Biology of Cancer Tumour volume doubling Single cell - 30 doublings 1 cm3 Lethal at 40 doublings - 1 kg Tumour growth is initially fast followed by growth deceleration Clinically doubling in tumour size over 2-3 months Tumour With Hypoxic Cells Biology of Metastasis Tumour acquires blood supply even before they are palpable early metastatic potential Cure of cancer must include attempt to eradicate primary completely attempt to eradicate metastasis Biology of Metastasis Active or passive dissemination of neoplastic disease from primary to distant site change enables cells to enter circulation adherence to endothelial walls extravasation invasion of stroma Biology of Metastasis Haematogenous spread most tumour cell in bloodstream are rapidly destroyed < 0.1% of cells survive to invade surviving cells are selected resistant subpopulation of primary tumour Subpopulation characteristics for metastasis destruction of basement membrane to enter vessel survival of blood turbulence appropriate ligand for cell adhesion molecule motility ability degradative enzymes - collengenase type IV Biology of Metastasis Subpopulation characteristics for metastasis successful tumours can grow to 1-2 mm further growth requires acquisition of blood supply angiogenesis is active process requiring tumour angiogenic factors Highly vascular tumours have increased potential for metastasis - more likely that suitable cell will eventually enter blood stream Biology of Metastasis Lymphatic spread Host invasion causes lymphatic vessel penetration Tumour emboli may get trapped in first node or bypass to more distant node - skip lesion Lymph nodes react to tumour and enlarge Are nodes a barrier/filter ? Lymphatic /vascular anastomosis exist nodal enlargement is a marker for dissemination Blood Supply of the Colon Biology of Cancer Mortality from cancer Local tumour effect Metastatic disease Systemic effects malnutrition depression of immunocompetence cytolkine/other compound release Understanding each tumour natural history is essential for therapy planning e.g. difference in breast Ca and head/neck Ca Biology of Cancer Mortality from cancer Local tumour effect Metastatic disease Systemic effects malnutrition depression of immunocompetence cytolkine/other compound release Understanding each tumour natural history is essential for therapy planning e.g. difference in breast Ca and head/neck Ca Importance of Early Detection of Tumours Too early for mutation to cells that can spread - eradicated before metastasis Treatment may reduce tumour bulk enough for immune system to manage Too early to acquire resistance to chemotherapy Screening for Tumours High incidence population Population at risk Sensitive, cheap non invasive tests Hep B carriers - HCC APC gene and FAP racial - Japanese and stomach cancer Familial breast cancer pap smear, faecal occult blood, mammogram Early stage of tumour - treatment makes a difference Screening for Tumours Lead Time Bias diagnosis made earlier, prognosis not made better Length Bias slow growing tumours, longer preclinical stage Self Selection Bias persons who present themselves for screening cf. The general population Surgical Principles Diagnosis Staging Fitness for surgery / treatment Surgery and or other treatment Surgical Principles Methods of Diagnosis Fine needle aspiration Histology incision excision luminal percutaneous wide bore needle - guided by imaging Tumour markers Window for FNA Luminal biopsy Luminal biopsy Laparoscopic Biopsy Lap Biopsy of Liver Lesion Surgical Principles Staging - UICC normenclature T -tumour N- nodal status M - metastasis The T,N,M is transcribed to a stage group I, II, III, IV Mucosa Submucosa Muscularis propria Pericolic perirectal tissue Subserosa Serosa Mucosa Submucosa Muscularis propria Subserosa Serosa Surgical Principles Stage Groups I - early treatable II - early treatable (nodes +ve) III - locally advanced IV - Metastatic Stage I & II : early - curative approach Stage III : locally advanced - potential for cure Stage IV : systemic - palliation Surgical Principles Staging Clinical Imaging Intraoperative Pathological - pTMN Surgical Principles Fitness for surgery/treatment CVS, Renal, endocrine, Resp., haematopoetic Additional test if warranted e.g. 2D ECHO Specific situations Liver - Childs grade Thorax - spirometry, blood gases Major Treatment Modalities Surgery Ionising radiation - RT - Radiotherapy Chemotherapy Hormonal Therapy Immunotherapy Principles of Surgical Oncology Radical surgery alone replaced by multimodality approach Lymph node involvement Appreciation of early metastatic potential Risk of tumour margins Marker of metastatic disease - phenotype capable of producing metastasis is present Survival in node positive is disease is half node negative disease Malignancies don’t always spread stepwise primary lymph nodes distant sites Principles of Surgical Oncology Survival has improved with less radical surgery early detection treatment modalities for metastasis Surgical Principles Surgeon must understand natural history pattern of mets failure patterns Decision aim of treatment - cure or palliation need for other modalities timing of different modalities Surgical Principles Surgery may be for primary disease eradication - radical operation secondary eradication or debulking palliation such as bypass, palliative resection Radical operation removal of tumour completely removal of wide margin of normal tissue removal of primary draining lymphatics obey oncological principles Radical Wipple operation Operative specimen - Wipple Operation Gastrojejunostomy for Palliation Radiotherapy Ionizing radiation - photons and electrons higher energy ® deeper penetration destroys important molecules e.g. DNA, reaction with water produces free radicals damage of DNA and other molecules unit of energy is the gray Gy = 100 rad delivered by brachytherapy or teletherapy In general for local control of neoplasm Ionizing radiation Multiplying tumour cells are sensitive G0 tumour cells protected • Cells at centre of solid tumour • Ischemic cells • Hypoxic cells Multiplying normal tissue at risk • skin, GI mucosa, bone marrow, germ cells Quiescent normal tissue not sensitive • Bone, liver Tumour With Hypoxic Cells RT- Increasing dose kills more tumour cells as well as normal tissue RT - Tumour destruction vs organ complications - probability curves Radiotherapy Fractionation Total dose given in series of small doses Reduces damage to normal tissue Maximises tumour killing Radiotherapy Fractionation – how does it work ? Each doses kills sensitive cells but spares G0 cells Reoxygenation of remnant G0 cells makes them divide and be susceptible tumour each fraction kills more cells Normal tissue is spared due to repair after each small sublethal dose – minimise complications Radiotherapy With Surgery Surgery removes tumour but margins are at risk for seeding Wider surgery increases complications RT excellent for margins (oxygen rich) poor for center of tumour (oxygen poor) Combination of surgery followed by RT increases probability of free margins and reduces local recurrence Principles of Chemotherapy Tumour mass growth slows as tumour enlarges - cells at center die or remain dormant (G0) because of blood supply limitation Only dividing cells (growth fraction) are killed Growth fraction is maximum at 37% of max size Each dose of chemotherapy kills a fraction of total cells Principles of Chemotherapy Concept of log kill Suppose a patient has 10 mets of 1 cm3 each (109 cells) – total of 1010 cells. One cycle of drugs produces 1-log kill or 90% eradication 6 drug cycles will give 6-log kill or 99.9999% eradication Each met will then have 103 cells left clinically undetectable(complete remission) – but recurrence is likely Principles of Chemotherapy Concept of log kill If we start with smaller volume after 6 drug cycles we may have 102 cells per met Immune system may be able to mop up actual cure Principles of Chemotherapy Chemotherapy for solid tumours is most effective for small (early) tumours Not suitable for solid primaries Ideal for early metastasis In general ChemoRx is for systemic control after primary treatment Types of Chemotherapy Curative - for tumours with 100% growth fraction - blood malignancies Adjuvant - treatment of micrometastasis after curative treatment of primary by other modality usually surgery Neoadjuvant - given before definitive surgery Palliative - “control” of disseminated disease Administering Chemotherapy Select effective drug - consider toxicity Calculate dose needed - consider patient performance, co morbid conditions Suitable intervals to allow normal tissue to recover - esp. bone marrow Support patient and treat toxicity Compassion & Quality of Life Administering Chemotherapy Plant Alkaloids Antibiotics Alkylating Agents Antimetabolites Combination Chemotherapy prevents emergence of early resistance additively increase in cytotoxic potency Cancer Therapy Nutritional Care Hospice Care Pain Management