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