Principles of Cancer CareIntroductionIntroduction

Overall cancer incidence risingOverall cancer incidence rising breast, colon, lung, prostate,lymphomabreast, colon, lung, prostate,lymphoma

Some cancers have reduced incidenceSome cancers have reduced incidence cervix, stomach, endometrialcervix, stomach, endometrial

Second highest cause of mortalitySecond highest cause of mortality

Principles of Cancer CareTerminologyTerminology Neoplasia - new growthNeoplasia - new growth

malignant - uncontrolled growth and malignant - uncontrolled growth and disseminationdissemination

Hyperplasia - increased cell numberHyperplasia - increased cell number

Metaplasia - mature cell type replacement Metaplasia - mature cell type replacement

Dysplasia - altered epithelial cell size, shape Dysplasia - altered epithelial cell size, shape and orientation. CIS most severe formand orientation. CIS most severe form

Principles of Cancer CareCauses of NeoplasiaCauses of Neoplasia Immunodefficiency - transplant tumours, Immunodefficiency - transplant tumours,

KaposiKaposi

Familial - Breast cancer, MEN, Lynch, FAP,Familial - Breast cancer, MEN, Lynch, FAP,

Physical carcinogenesisPhysical carcinogenesis foreign body - asbestosforeign body - asbestos ionizing radiationionizing radiation

Chemical carcinogenesisChemical carcinogenesis

VirusesViruses

Biology of CancerClonalityClonality

Most tumours arise from a single Most tumours arise from a single altered cellaltered cell

Most transformed cells die or are Most transformed cells die or are destroyeddestroyed

Surviving cellSurviving cell heritabilityheritability escape from normal controlescape from normal control

Biology of CancerTumour volume doublingTumour volume doubling

Single cell - 30 doublings Single cell - 30 doublings 1 cm 1 cm33

Lethal at 40 doublings - 1 kgLethal at 40 doublings - 1 kg

Tumour growth is initially fast - Tumour growth is initially fast - followed by growth deceleration followed by growth deceleration

Clinically doubling in tumour size Clinically doubling in tumour size over 2-3 monthsover 2-3 months

Tumour With Hypoxic Cells

Biology of Metastasis Tumour acquires blood supply even Tumour acquires blood supply even

before they are palpable before they are palpable early early metastatic potential metastatic potential

Cure of cancer must include Cure of cancer must include attempt to eradicate primary completelyattempt to eradicate primary completely attempt to eradicate metastasisattempt to eradicate metastasis

Biology of MetastasisActive or passive dissemination of Active or passive dissemination of neoplastic disease from primary to neoplastic disease from primary to distant sitedistant site

change enables cells to enter circulationchange enables cells to enter circulation adherence to endothelial wallsadherence to endothelial walls extravasationextravasation invasion of stromainvasion of stroma

Biology of Metastasis

Haematogenous spreadHaematogenous spread most tumour cell in bloodstream are rapidly most tumour cell in bloodstream are rapidly

destroyeddestroyed < 0.1% of cells survive to invade< 0.1% of cells survive to invade surviving cells are selected resistant surviving cells are selected resistant

subpopulation of primary tumoursubpopulation of primary tumour

Subpopulation characteristics for metastasisSubpopulation characteristics for metastasis destruction of basement membrane to enter vesseldestruction of basement membrane to enter vessel survival of blood turbulencesurvival of blood turbulence appropriate ligand for cell adhesion moleculeappropriate ligand for cell adhesion molecule motility abilitymotility ability degradative enzymes - collengenase type IVdegradative enzymes - collengenase type IV

Biology of MetastasisSubpopulation characteristics for metastasisSubpopulation characteristics for metastasis successful tumours can grow to 1-2 mmsuccessful tumours can grow to 1-2 mm

further growth requires acquisition of blood further growth requires acquisition of blood supplysupply

angiogenesis is active process requiring angiogenesis is active process requiring tumour angiogenic factors tumour angiogenic factors

Highly vascular tumours have increased potential Highly vascular tumours have increased potential for metastasis - more likely that suitable cell will for metastasis - more likely that suitable cell will eventually enter blood streameventually enter blood stream

Biology of MetastasisLymphatic spreadLymphatic spread Host invasion causes lymphatic vessel Host invasion causes lymphatic vessel

penetrationpenetration Tumour emboli may get trapped in first node Tumour emboli may get trapped in first node

or bypass to more distant node - skip lesionor bypass to more distant node - skip lesion Lymph nodes react to tumour and enlargeLymph nodes react to tumour and enlarge Are nodes a barrier/filter ? Are nodes a barrier/filter ?

Lymphatic /vascular anastomosis existLymphatic /vascular anastomosis exist nodal enlargement is a marker for nodal enlargement is a marker for

disseminationdissemination

Blood Supply of the Colon

Biology of CancerMortality from cancer Mortality from cancer Local tumour effectLocal tumour effect Metastatic diseaseMetastatic disease Systemic effectsSystemic effects

malnutritionmalnutrition depression of immunocompetencedepression of immunocompetence cytolkine/other compound releasecytolkine/other compound release

Understanding each tumour natural history is Understanding each tumour natural history is essential for therapy planningessential for therapy planning

e.g. difference in breast Ca and head/neck Cae.g. difference in breast Ca and head/neck Ca

Biology of CancerMortality from cancer Mortality from cancer Local tumour effectLocal tumour effect Metastatic diseaseMetastatic disease Systemic effectsSystemic effects

malnutritionmalnutrition depression of immunocompetencedepression of immunocompetence cytolkine/other compound releasecytolkine/other compound release

Understanding each tumour natural history is Understanding each tumour natural history is essential for therapy planningessential for therapy planning

e.g. difference in breast Ca and head/neck e.g. difference in breast Ca and head/neck CaCa

Importance of Early Detection of Tumours

Too early for mutation to cells that can Too early for mutation to cells that can spread - eradicated before metastasisspread - eradicated before metastasis

Treatment may reduce tumour bulk Treatment may reduce tumour bulk enough for immune system to manageenough for immune system to manage

Too early to acquire resistance to Too early to acquire resistance to chemotherapychemotherapy

Screening for Tumours High incidence populationHigh incidence population Population at riskPopulation at risk

Hep B carriers - HCCHep B carriers - HCC APC gene and FAPAPC gene and FAP racial - Japanese and stomach cancerracial - Japanese and stomach cancer Familial breast cancerFamilial breast cancer

Sensitive, cheap non invasive testsSensitive, cheap non invasive tests pap smear, faecal occult blood, mammogrampap smear, faecal occult blood, mammogram

Early stage of tumour - treatment makes a Early stage of tumour - treatment makes a differencedifference

Screening for TumoursLead Time BiasLead Time Bias

diagnosis made earlier, prognosis not diagnosis made earlier, prognosis not made bettermade better

Length BiasLength Bias slow growing tumours, longer slow growing tumours, longer

preclinical stagepreclinical stage

Self Selection BiasSelf Selection Bias persons who present themselves for persons who present themselves for

screening cf. The general population screening cf. The general population

Surgical Principles

DiagnosisDiagnosis

Staging Staging

Fitness for surgery / treatmentFitness for surgery / treatment

Surgery and or other treatmentSurgery and or other treatment

Surgical PrinciplesMethods of DiagnosisMethods of Diagnosis Fine needle aspirationFine needle aspiration

HistologyHistology incisionincision excisionexcision luminalluminal percutaneous wide bore needle percutaneous wide bore needle

- guided by imaging- guided by imaging

Tumour markersTumour markers

Window for FNA

Luminal biopsy

Luminal biopsy

Laparoscopic Biopsy

Lap Biopsy of Liver Lesion

Surgical PrinciplesStaging - UICC normenclatureStaging - UICC normenclature

T -tumourT -tumour N- nodal statusN- nodal status M - metastasis M - metastasis

The T,N,M is transcribed to a The T,N,M is transcribed to a stage group I, II, III, IVstage group I, II, III, IV

PericolicPericolicperirectalperirectal

tissuetissue

MucosaMucosa

SubmucosaSubmucosa

Muscularis propriaMuscularis propria

SubserosaSubserosa

SerosaSerosa

MucosaMucosa

SubmucosaSubmucosa

Muscularis propriaMuscularis propria

SubserosaSubserosa

SerosaSerosa

Surgical Principles Stage GroupsStage Groups

I - early treatableI - early treatable II - early treatable (nodes +ve) II - early treatable (nodes +ve) III - locally advanced III - locally advanced IV - MetastaticIV - Metastatic

Stage I & IIStage I & II : : early - curative early - curative approachapproach

Stage IIIStage III :: locally locally advanced - potential for cureadvanced - potential for cure

Stage IVStage IV :: systemic - systemic - palliationpalliation

Surgical Principles

StagingStaging

ClinicalClinical

ImagingImaging

IntraoperativeIntraoperative

Pathological - pTMNPathological - pTMN

Surgical PrinciplesFitness for surgery/treatmentFitness for surgery/treatment

CVS, Renal, endocrine, Resp., haematopoetic CVS, Renal, endocrine, Resp., haematopoetic

Additional test if warranted e.g. 2D ECHOAdditional test if warranted e.g. 2D ECHO

Specific situations - Specific situations - Liver - Childs gradeLiver - Childs grade Thorax - spirometry, blood gasesThorax - spirometry, blood gases

Major Treatment Modalities SurgerySurgery

Ionising radiation - RT - Ionising radiation - RT - RadiotherapyRadiotherapy

ChemotherapyChemotherapy

Hormonal TherapyHormonal Therapy

ImmunotherapyImmunotherapy

Principles of Surgical Oncology

Radical surgery alone replaced by Radical surgery alone replaced by multimodality approachmultimodality approach Appreciation of early metastatic potentialAppreciation of early metastatic potential Risk of tumour marginsRisk of tumour margins

Lymph node involvementLymph node involvement Marker of metastatic disease - phenotype Marker of metastatic disease - phenotype

capable of producing metastasis is presentcapable of producing metastasis is present

Survival in node positive is disease is half Survival in node positive is disease is half node negative diseasenode negative disease

Malignancies don’t always spread stepwiseMalignancies don’t always spread stepwise primary primary lymph nodes lymph nodes distant sites distant sites

Principles of Surgical Oncology Survival has improved with Survival has improved with less radical surgeryless radical surgery early detectionearly detection treatment modalities for metastasistreatment modalities for metastasis

Surgical Principles Surgeon must understandSurgeon must understand

natural historynatural history pattern of metspattern of mets failure patternsfailure patterns

DecisionDecision aim of treatment - cure or palliationaim of treatment - cure or palliation need for other modalitiesneed for other modalities timing of different modalitiestiming of different modalities

Surgical Principles Surgery may be for Surgery may be for

primary disease eradication - radical primary disease eradication - radical operationoperation

secondary eradication or debulkingsecondary eradication or debulking palliation such as bypass, palliative resectionpalliation such as bypass, palliative resection

Radical operationRadical operation removal of tumour completelyremoval of tumour completely removal of wide margin of normal tissueremoval of wide margin of normal tissue removal of primary draining lymphaticsremoval of primary draining lymphatics obey oncological principlesobey oncological principles

RadicalWipple operation

Operative specimen - Wipple Operation

Gastrojejunostomy for Palliation

Radiotherapy Ionizing radiation - photons and electronsIonizing radiation - photons and electrons

higher energy ® deeper penetrationhigher energy ® deeper penetration destroys important molecules e.g. DNA, destroys important molecules e.g. DNA, reaction with water produces free radicals reaction with water produces free radicals

damage of DNA and other molecules damage of DNA and other molecules unit of energy is the gray Gy = 100 radunit of energy is the gray Gy = 100 rad delivered by brachytherapy or teletherapydelivered by brachytherapy or teletherapy

In general for local control of neoplasmIn general for local control of neoplasm

Ionizing radiation Multiplying tumour cells are sensitiveMultiplying tumour cells are sensitive G0 tumour cells protectedG0 tumour cells protected

• Cells at centre of solid tumourCells at centre of solid tumour• Ischemic cellsIschemic cells• Hypoxic cellsHypoxic cells

Multiplying normal tissue at riskMultiplying normal tissue at risk• skin, GI mucosa, bone marrow, germ cells skin, GI mucosa, bone marrow, germ cells

Quiescent normal tissue not sensitiveQuiescent normal tissue not sensitive• Bone, liverBone, 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 Fractionation

Total dose given in series of small dosesTotal dose given in series of small doses

Reduces damage to normal tissueReduces damage to normal tissue

Maximises tumour killing Maximises tumour killing

Radiotherapy

Fractionation – how does it work ?Fractionation – how does it work ? Each doses kills sensitive cells but spares Each doses kills sensitive cells but spares

G0 cellsG0 cells Reoxygenation of remnant G0 cells makes Reoxygenation of remnant G0 cells makes

them divide and be susceptible tumour - them divide and be susceptible tumour - each fraction kills more cellseach fraction kills more cells

Normal tissue is spared due to repair after Normal tissue is spared due to repair after each small sublethal dose – minimise each small sublethal dose – minimise complicationscomplications

Radiotherapy With Surgery Surgery removes tumour but margins are Surgery removes tumour but margins are

at risk for seedingat risk for seeding

Wider surgery increases complicationsWider surgery increases complications

RT excellent for margins (oxygen rich) RT excellent for margins (oxygen rich) poor for center of tumour (oxygen poor) poor for center of tumour (oxygen poor)

Combination of surgery followed by RT Combination of surgery followed by RT increases probability of free margins and increases probability of free margins and reduces local recurrencereduces local recurrence

Principles of Chemotherapy Tumour mass growth slows as tumour Tumour mass growth slows as tumour

enlarges - cells at center die or remain enlarges - cells at center die or remain dormant (G0) because of blood supply dormant (G0) because of blood supply limitation limitation

Only dividing cells (growth fraction) are Only dividing cells (growth fraction) are killedkilled

Growth fraction is maximum at 37% of Growth fraction is maximum at 37% of max sizemax size

Each dose of chemotherapy kills a fraction Each dose of chemotherapy kills a fraction of total cells of total cells

Principles of ChemotherapyConcept of log killConcept of log kill Suppose a patient has 10 mets of 1 cmSuppose a patient has 10 mets of 1 cm33 each each

(10(1099 cells) – total of 10 cells) – total of 101010 cells. cells. One cycle of drugs produces 1-log kill or One cycle of drugs produces 1-log kill or

90% eradication90% eradication 6 drug cycles will give 6-log kill or 6 drug cycles will give 6-log kill or

99.9999% eradication99.9999% eradication Each met will then have 10Each met will then have 1033 cells left - cells left -

clinically undetectable(complete remission) clinically undetectable(complete remission) – but recurrence is likely– but recurrence is likely

Principles of ChemotherapyConcept of log killConcept of log kill

If we start with smaller volume after 6 If we start with smaller volume after 6 drug cycles we may have 10drug cycles we may have 1022 cells per cells per met met

Immune system may be able to mop up - Immune system may be able to mop up - actual cureactual cure

Principles of Chemotherapy Chemotherapy for solid tumours is most Chemotherapy for solid tumours is most

effective for small (early) tumourseffective for small (early) tumours

Not suitable for solid primaries Not suitable for solid primaries

Ideal for early metastasisIdeal for early metastasis

In general ChemoRx is for systemic In general ChemoRx is for systemic control after primary treatmentcontrol after primary treatment

Types of Chemotherapy

Curative - for tumours with 100% growth Curative - for tumours with 100% growth fraction - blood malignanciesfraction - blood malignancies

Adjuvant - treatment of micrometastasis after Adjuvant - treatment of micrometastasis after curative treatment of primary by other curative treatment of primary by other modality usually surgerymodality usually surgery

Neoadjuvant - given before definitive Neoadjuvant - given before definitive surgerysurgery

Palliative - “control” of disseminated diseasePalliative - “control” of disseminated disease

Administering Chemotherapy

Select effective drug - consider toxicitySelect effective drug - consider toxicity

Calculate dose needed - consider patient Calculate dose needed - consider patient performance, co morbid conditionsperformance, co morbid conditions

Suitable intervals to allow normal tissue Suitable intervals to allow normal tissue to recover - esp. bone marrowto recover - esp. bone marrow

Support patient and treat toxicitySupport patient and treat toxicity

Compassion & Quality of LifeCompassion & Quality of Life

Administering Chemotherapy

Plant AlkaloidsPlant Alkaloids

AntibioticsAntibiotics

Alkylating AgentsAlkylating Agents

AntimetabolitesAntimetabolites

Combination ChemotherapyCombination Chemotherapy prevents emergence of early resistanceprevents emergence of early resistance additively increase in cytotoxic additively increase in cytotoxic

potencypotency

Cancer Therapy

Nutritional CareNutritional Care

Hospice CareHospice Care

Pain ManagementPain Management