oncology lmcc refresher course
DESCRIPTION
Oncology LMCC Refresher Course. Dr. Garth Nicholas. Outline. How Big A Problem? Cells and Molecules Risk Factors and Screening Diagnosis and Staging Treatments Specific Cancers. How Big A Problem?. 145 500 new cancers in Canada in 2004 68 300 cancer deaths in 2004 - PowerPoint PPT PresentationTRANSCRIPT
Oncology Oncology
LMCC Refresher CourseLMCC Refresher Course
Dr. Garth NicholasDr. Garth Nicholas
OutlineOutline
How Big A Problem?How Big A Problem? Cells and MoleculesCells and Molecules Risk Factors and ScreeningRisk Factors and Screening Diagnosis and StagingDiagnosis and Staging TreatmentsTreatments Specific CancersSpecific Cancers
How Big A Problem?How Big A Problem?
145 500 new cancers in Canada in 145 500 new cancers in Canada in 20042004
68 300 cancer deaths in 200468 300 cancer deaths in 2004 Projected to be the commonest Projected to be the commonest
cause of death in Canadians by 2010.cause of death in Canadians by 2010.
How Big A Problem?How Big A Problem?
Lifetime risk of developing cancer for Lifetime risk of developing cancer for CanadiansCanadians– WomenWomen 38%38%– MenMen 43%43%
31% of PYLL due to cancer (954 000 31% of PYLL due to cancer (954 000 years)years)
65% of diagnoses and 80% of deaths 65% of diagnoses and 80% of deaths are in people over the age of 60are in people over the age of 60
Canadian New Cases and Canadian New Cases and DeathsDeaths
TumourTumour New New CasesCases
DeathsDeaths Case-Case-Fatality Fatality RateRate
LungLung 1990019900 1690016900 0.850.85
BreastBreast 1980019800 49004900 0.250.25
ColonColon 1640016400 65606560 0.400.40
ProstateProstate 1610016100 27372737 0.170.17
NHLNHL 68006800 27202720 0.400.40
Women Men
Women Men
Cells and MoleculesCells and Molecules
Cancer:Cancer:– Characterized by growth and division of Characterized by growth and division of
cells outside the control of normal cells outside the control of normal regulatory mechanismsregulatory mechanisms
– Characterized as benign or malignant by Characterized as benign or malignant by their capacity for metastasistheir capacity for metastasis
– Benign tumours designated by the suffix -Benign tumours designated by the suffix -omaoma
– Malignant tumours are divided most Malignant tumours are divided most broadly into carcinomas and sarcomas, broadly into carcinomas and sarcomas, and blastomas in childrenand blastomas in children
Exceptions to the nomenclature Exceptions to the nomenclature rules:rules:– HepatomaHepatoma– MelanomaMelanoma– LeukemiaLeukemia– GlioblastomaGlioblastoma
CarcinomasCarcinomas
CarcinomasCarcinomas– Arise from epitheliumArise from epithelium– Commonest are adenocarcinoma and Commonest are adenocarcinoma and
squamous carcinomasquamous carcinoma– Many others, including germ cell Many others, including germ cell
tumours, transitional cell carcinomas, tumours, transitional cell carcinomas, large cell carcinoma,large cell carcinoma, neuroendocrine neuroendocrine carcinomacarcinoma
CarcinomasCarcinomas
AdenocarcinomaAdenocarcinoma– BreastBreast– LungLung– ProstateProstate– Most GI, including colonMost GI, including colon– Endocrine malignanciesEndocrine malignancies– Characterized by gland formationCharacterized by gland formation
CarcinomasCarcinomas
Squamous carcinomaSquamous carcinoma– Head and neck cancersHead and neck cancers– LungLung– SkinSkin– CervixCervix– EsophagusEsophagus– AnusAnus
CarcinomasCarcinomas
Germ Cell TumoursGerm Cell Tumours– Most commonly testicular cancersMost commonly testicular cancers– Ovarian Ovarian – Primary mediastinalPrimary mediastinal– Histologic subtypes include teratomas, Histologic subtypes include teratomas,
embryonal carcinomas, yolk sac embryonal carcinomas, yolk sac tumourstumours
SarcomasSarcomas
– Much rarer than carcinomasMuch rarer than carcinomas– Arise from parenchymal tissueArise from parenchymal tissue– About 800 soft-tissue sarcomas per year About 800 soft-tissue sarcomas per year
in Canada, and fewer bone sarcomasin Canada, and fewer bone sarcomas– Named for the tissue they arise from, Named for the tissue they arise from,
when knownwhen known
SarcomasSarcomas
– Known tissues of originKnown tissues of origin LiposarcomaLiposarcoma FatFat RhabdomyosarcomaRhabdomyosarcoma Striated muscleStriated muscle LeiomyosarcomaLeiomyosarcoma Smooth muscleSmooth muscle OsteosarcomaOsteosarcoma BoneBone ChondrosarcomaChondrosarcoma CartilageCartilage
– Unknown tissue of originUnknown tissue of origin Malignant fibrous histiocytoma, Ewing’s Malignant fibrous histiocytoma, Ewing’s
Sarcoma, alveolar soft parts tumourSarcoma, alveolar soft parts tumour
OthersOthers
Hematologic malignanciesHematologic malignancies– Do not fit well into the Do not fit well into the
carcinoma/sarcoma spectrumcarcinoma/sarcoma spectrum– Technically, lymphomas are considered Technically, lymphomas are considered
sarcomas (reticulosarcoma) while sarcomas (reticulosarcoma) while leukemias are considered carcinomasleukemias are considered carcinomas
– Practically, no one makes this distinctionPractically, no one makes this distinction
BlastomasBlastomas
Aggressive childhood tumoursAggressive childhood tumours– Neuroblastoma, retinoblastoma, Neuroblastoma, retinoblastoma,
medulloblastomamedulloblastoma– Named for their histologic resemblance Named for their histologic resemblance
to cells at the centre of blastocytesto cells at the centre of blastocytes
SummarySummary
Histologic characteristics of cancerHistologic characteristics of cancer– Excessive cellularityExcessive cellularity– Disrupted architectureDisrupted architecture– Frequent mitoses, sometimes bizarreFrequent mitoses, sometimes bizarre– Unusual cell appearanceUnusual cell appearance
Large, hyperchromatic nucleiLarge, hyperchromatic nuclei
– Varying degrees of differentiationVarying degrees of differentiation– Invasion into surrounding tissueInvasion into surrounding tissue
Genetic ChangesGenetic Changes
Cancers arise due to changes in a Cancers arise due to changes in a cell’s genetic machinerycell’s genetic machinery
These changes involve genes that These changes involve genes that are divided into two major groupsare divided into two major groups– OncogenesOncogenes– Tumour suppressor genesTumour suppressor genes
Genetic ChangesGenetic Changes
OncogenesOncogenes– Are altered forms of normal genes called Are altered forms of normal genes called
proto-oncogenesproto-oncogenes– Genes have dominant transforming Genes have dominant transforming
properties: one abnormal copy is properties: one abnormal copy is sufficientsufficient
– Proto-oncogenes tend to function in Proto-oncogenes tend to function in normal cell cycling and differentiationnormal cell cycling and differentiation
– Mutation or overexpression leads to Mutation or overexpression leads to unregulated cell divisionunregulated cell division
Genetic ChangesGenetic Changes
Tumour Suppressor GenesTumour Suppressor Genes– Genes which are normally involved in the Genes which are normally involved in the
negative regulation of cell cyclingnegative regulation of cell cycling– Genes have recessive transforming Genes have recessive transforming
properties: both copies must be properties: both copies must be abnormalabnormal
– Classic example is retinoblastomaClassic example is retinoblastoma– Loss of these genes allows cells to Loss of these genes allows cells to
proliferate unregulated, or with reduced proliferate unregulated, or with reduced restraints restraints
Genetic ChangesGenetic Changes
CML is driven by CML is driven by the bcr-abl the bcr-abl oncogene oncogene (Philadelphia (Philadelphia chromosome)chromosome)
Genetic ChangesGenetic Changes
Genetic ChangesGenetic Changes
In reality, single mutations are In reality, single mutations are usually insufficient for malignant usually insufficient for malignant transformation, and cancer cells transformation, and cancer cells contain a number of genetic contain a number of genetic abnormalities, many of uncertain abnormalities, many of uncertain significancesignificance
Risk FactorsRisk Factors
Risk factors for cancer are difficult to Risk factors for cancer are difficult to studystudy– Long interval between exposure and diseaseLong interval between exposure and disease– Many exposures to agents of unknown Many exposures to agents of unknown
significancesignificance– Unclear correlation between carcinogenesis Unclear correlation between carcinogenesis
in laboratory and in real worldin laboratory and in real world ?Threshold levels for carcinogenesis?Threshold levels for carcinogenesis
– IARC publishes a list of known causes of IARC publishes a list of known causes of cancer, and estimates of their significancecancer, and estimates of their significance
Risk FactorsRisk Factors
Factor TypeFactor Type Attributable RiskAttributable Risk
EnvironmentalEnvironmental 5%5%
LifestyleLifestyle 45%45%
OccupationalOccupational 4%4%
PharmacologicPharmacologic 2%2%
BiologicBiologic 4%4%
Risk FactorsRisk Factors
Environmental CausesEnvironmental Causes– AflatoxinAflatoxin Hepatocellular carcinomaHepatocellular carcinoma– ErioniteErionite MesotheliomaMesothelioma– RadonRadon Lung (RR=2)Lung (RR=2)– Solar RadiationSolar RadiationMelanoma (RR=3)Melanoma (RR=3)
Risk FactorsRisk Factors
Lifestyle CausesLifestyle Causes– TobaccoTobacco Lung (RR=12) Larynx (12) Oral Lung (RR=12) Larynx (12) Oral
cavity (5), esophagus(4), cavity (5), esophagus(4), kidney kidney (3), bladder (3), (3), bladder (3), pancreas (2)pancreas (2)
– Smokeless tobaccoSmokeless tobacco Oral Cavity (2)Oral Cavity (2)– Betel and tobaccoBetel and tobacco Oral Cavity (9)Oral Cavity (9)– AlcoholAlcohol Oral cavity (5), esophagus(4), Oral cavity (5), esophagus(4),
larynx (3) liver (3)larynx (3) liver (3)– DietDiet
Risk FactorsRisk Factors
Occupational (35 factors listed)Occupational (35 factors listed)– BenzeneBenzene Leukemia (RR=3)Leukemia (RR=3)– AsbestosAsbestos Mesothelioma (6), lung (3)Mesothelioma (6), lung (3)
Pharmacologic (18 factors listed)Pharmacologic (18 factors listed)– Alkylating agents (9)Alkylating agents (9) LeukemiasLeukemias– Immunosuppressants(2)Immunosuppressants(2) LymphomasLymphomas– Hormones (5)Hormones (5) EndometriumEndometrium– Others (2)Others (2)
Risk FactorsRisk Factors
Biologic CausesBiologic Causes– EBVEBV Burkitt’s lymphoma (RR=30)Burkitt’s lymphoma (RR=30)– H. pyloriH. pylori Gastric (4)Gastric (4)– HBVHBV Liver (100)Liver (100)– HCVHCV Liver (20)Liver (20)– HIVHIV KS (1000), NHL (100) KS (1000), NHL (100) – HPV t16,18HPV t16,18 Cervix (20)Cervix (20)– HTLV-1HTLV-1 Adult T-cell lymphoma (4)Adult T-cell lymphoma (4)– O. viverriniO. viverrini Cholangiocarcinoma (5)Cholangiocarcinoma (5)– S. haematobiliumS. haematobilium Bladder (5)Bladder (5)
ScreeningScreening
Screening is the routine testing of Screening is the routine testing of asymptomatic individuals for the asymptomatic individuals for the presence of cancerpresence of cancer
Underlying screening is the Underlying screening is the assumption that cancers detected at assumption that cancers detected at the asymptomatic stage are more the asymptomatic stage are more amenable to therapy amenable to therapy
ScreeningScreening
Cancers commonly screened for in Cancers commonly screened for in adults are:adults are:– Breast (mammography)Breast (mammography)– Cervix (Pap smears)Cervix (Pap smears)– Colon (Barium enema/colonoscopy/FOBT)Colon (Barium enema/colonoscopy/FOBT)– Prostate (PSA)Prostate (PSA)
Evidence behind screening is Evidence behind screening is surprisingly contentious, in part surprisingly contentious, in part because of the difficulty of designing because of the difficulty of designing studies to avoid biasstudies to avoid bias
ScreeningScreening
Lead-time BiasLead-time Bias
Time
Cancer starts
Symptoms
Diagnosis and treatment Death
Diagnosis by screening
Treatment
Cancer becomes incurable
ScreeningScreening
Length Time BiasLength Time Bias
1 2 3 4
*
*
**
*
**
**
ScreeningScreening
BreastBreast– Recommendations are for annual breast Recommendations are for annual breast
exam and biannual mammography starting exam and biannual mammography starting at age 50 (?ending at age 74)at age 50 (?ending at age 74)
CervixCervix– Recommend Pap smears annually for first Recommend Pap smears annually for first
three years after becoming sexually active, three years after becoming sexually active, then every two years until age 70then every two years until age 70
– Frequency is different if any test is Frequency is different if any test is abnormalabnormal
ScreeningScreening
ProstateProstate– Ontario guidelines state that “Ontario guidelines state that “Healthy men Healthy men
without symptoms may decide to have a without symptoms may decide to have a PSA test after talking to their family doctor PSA test after talking to their family doctor or if they are at high risk for prostate or if they are at high risk for prostate cancer ("first degree" relatives with the cancer ("first degree" relatives with the disease, men of African ancestry).”disease, men of African ancestry).”
– Not covered by OHIP because no trial has Not covered by OHIP because no trial has ever shown a survival advantage to ever shown a survival advantage to screeningscreening
ScreeningScreening
ColonColon– Methods include fecal occult Methods include fecal occult
blood testing (FOBT), blood testing (FOBT), colonoscopy, Ba enema, colonoscopy, Ba enema, sigmoidoscopysigmoidoscopy
– Ontario is currently running a Ontario is currently running a pilot program of FOBT in 12 pilot program of FOBT in 12 areas to inform eventual areas to inform eventual development of a province-development of a province-wide policywide policy
– Other modalities are Other modalities are inconsistently used, and inconsistently used, and probably too expensive for probably too expensive for mass screeningmass screening
Why Not Screen for All Why Not Screen for All Cancers?Cancers?
Cancer-related factorsCancer-related factors
Preclinical interval too short
Cancer incurable, even if screen detected
Cancer Starts Symptoms Death
Cancer Starts Symptoms DeathIncurable
Incurable
Why Not Screen for All Why Not Screen for All Cancers?Cancers?
Test-related factorsTest-related factors– Test not sensitive/specific enoughTest not sensitive/specific enough– Test can’t be applied to whole Test can’t be applied to whole
populationpopulation Too expensiveToo expensive Insufficient infrastructure/personnelInsufficient infrastructure/personnel Unacceptable to majority of populationUnacceptable to majority of population
– Tumour not common enoughTumour not common enough
DiagnosisDiagnosis
Impossible to list all possible Impossible to list all possible symptoms of cancersymptoms of cancer
Systematically think about symptoms Systematically think about symptoms in four categories:in four categories:– Local symptoms of tumourLocal symptoms of tumour– Symptoms from regional (nodal) spreadSymptoms from regional (nodal) spread– Symptoms from metastatic spreadSymptoms from metastatic spread– Symptoms from paraneoplastic Symptoms from paraneoplastic
phenomenaphenomena
DiagnosisDiagnosis
Local SymptomsLocal Symptoms– Lung Lung
cough, hemoptysis, SOB, chest wall paincough, hemoptysis, SOB, chest wall pain
– ProstateProstate urinary obstruction, hematuriaurinary obstruction, hematuria
– LeukemiaLeukemia Symptoms of marrow replacement, Symptoms of marrow replacement,
cytopeniascytopenias
– BreastBreast Breast mass, bleeding from nippleBreast mass, bleeding from nipple
DiagnosisDiagnosis
Symptoms from regional (nodal) Symptoms from regional (nodal) spreadspread– Lung (mediastinal nodes)Lung (mediastinal nodes)
SVCO, esophageal obstruction, hoarse voice, SVCO, esophageal obstruction, hoarse voice, etcetc
– Breast (axillary nodes)Breast (axillary nodes) Lump under armLump under arm
DiagnosisDiagnosis
Symptoms from Metastatic SpreadSymptoms from Metastatic Spread– LiverLiver
Jaundice, abnormal LFT, painJaundice, abnormal LFT, pain
– BrainBrain Focal neurologic symptoms, seizuresFocal neurologic symptoms, seizures
– LungLung Cough, SOB, hemoptysisCough, SOB, hemoptysis
– BoneBone Pain, pathologic fracture, elevated Alk PhosPain, pathologic fracture, elevated Alk Phos
DiagnosisDiagnosis
Paraneoplastic SyndromesParaneoplastic Syndromes– Common, non-specificCommon, non-specific
Poor appetite, weight loss, DVTPoor appetite, weight loss, DVT
– Hormonal syndromesHormonal syndromes SIADH, Cushing’s, hypercalcemia, carcinoidSIADH, Cushing’s, hypercalcemia, carcinoid
– Neurologic syndromesNeurologic syndromes Lambert-Eaton Syndrome, demyelination Lambert-Eaton Syndrome, demyelination
syndromessyndromes
DiagnosisDiagnosis
Ultimately, diagnosis requires Ultimately, diagnosis requires tissuetissue– Fine needle aspirateFine needle aspirate– Core biopsyCore biopsy– Excisional biopsyExcisional biopsy– Open biopsyOpen biopsy
StagingStaging
The second part of diagnosis is stagingThe second part of diagnosis is staging Purposes of stagingPurposes of staging
– Group similar patients togetherGroup similar patients together– Determine intent of treatmentDetermine intent of treatment– Prognostic purposesPrognostic purposes
Standard staging tests vary by cancer, Standard staging tests vary by cancer, but may include bone scans, marrow but may include bone scans, marrow biopsy, imaging of biopsy, imaging of brain/thorax/abdomenbrain/thorax/abdomen
StagingStaging
Most cancers are staged with a TNM Most cancers are staged with a TNM staging system, which leads to staging system, which leads to overall stage I-IVoverall stage I-IV– TTumourumour– NNodalodal– MMetastasesetastases
StagingStaging
Breast CancerBreast CancerT1 1-20 mmT2 20-50 mmT3 >50 mmT4 Chest wall, skin,
or inflammatory
N0 No NodesN1 Mobile axillary nodesN2 Fixed Axillary NodesN3 Internal Mammery Nodes
M0 No distant metastasesM1 Distant metastases present
StagingStaging
T N M Stage1 0 0 11 1 0 2A2 0 0 2A2 1 0 2B3 0 0 2B3 1 0 3AAny 2 0 3A4 Any 0 3BAny 3 0 3BAny Any 1 4
Only people who work with cancer every day actually memorize these.
StagingStaging Another staging system worth remembering is Another staging system worth remembering is
the Ann Arbour stages for Hodgkin’s diseasethe Ann Arbour stages for Hodgkin’s disease
Stage DefinitionI Involvement of a single node regionII Two or more node regions on same side of diaphragmIII Lymph node regions on both sides of the diaphragmIV Involvement of one or more extranodal sites in addition to the
site for which the suffix “E” is used (see below)
Suffix A Absence of “B Symptoms”B Presence of “B Symptoms”: fever, drenching night sweats,
loss of >10% body weight in preceeding 6 monthsE Involvement of single extranodal site contiguous with nodal
diseaseX Bulky disease (nodal mass >10 cm, or mediastinum widened
>1/3)
TreatmentTreatment
Intent of TreatmentIntent of Treatment– Radical vs. PalliativeRadical vs. Palliative– AdjuvantAdjuvant– NeoadjuvantNeoadjuvant
Modalities of TreatmentModalities of Treatment– SurgerySurgery– RadiotherapyRadiotherapy– Systemic therapySystemic therapy
Treatment: SurgeryTreatment: Surgery Indications for SurgeryIndications for Surgery
– Obtain tissue for diagnosis/stagingObtain tissue for diagnosis/staging– Definitive treatment of primary tumourDefinitive treatment of primary tumour– Palliation of obstructive/mass effect Palliation of obstructive/mass effect
symptomssymptoms– Cancer prophylaxis in high-risk casesCancer prophylaxis in high-risk cases
Esophageal dysplasia/BRCA/FAP/ulcerative Esophageal dysplasia/BRCA/FAP/ulcerative colitiscolitis
– Support other proceduresSupport other procedures Central venous accessCentral venous access
– Rehabilitation/reconstructionRehabilitation/reconstruction
Treatment: SurgeryTreatment: Surgery
Surgery has a central role, as 90% of Surgery has a central role, as 90% of solid tumours that are cured have solid tumours that are cured have surgery as part of the treatment plansurgery as part of the treatment plan
Appropriate primary cancer surgery Appropriate primary cancer surgery includes resection of primary tumour includes resection of primary tumour and associated lymphatic drainage and associated lymphatic drainage
Surgical debulking is appropriate in Surgical debulking is appropriate in only a tiny minority of casesonly a tiny minority of cases– Ovarian cancer, Burkitt’s lymphomaOvarian cancer, Burkitt’s lymphoma
Treatment: SurgeryTreatment: Surgery
In few cases is it appropriate to In few cases is it appropriate to resect metastatic disease:resect metastatic disease:– Solitary brain metastasesSolitary brain metastases– Anatomically amenable liver metastases Anatomically amenable liver metastases
from colon cancerfrom colon cancer– Pulmonary metastases from sarcomasPulmonary metastases from sarcomas– Residual disease in germ cell tumoursResidual disease in germ cell tumours
Treatment: RadiationTreatment: Radiation
Ionizing radiation delivered to tumour and Ionizing radiation delivered to tumour and surrounding tissuesurrounding tissue– TeletherapyTeletherapy– BrachytherapyBrachytherapy– Systemically administered agentsSystemically administered agents
Not understood exactly how radiation Not understood exactly how radiation causes cell deathcauses cell death– DNA likely targetDNA likely target– Differential ability of tumour and normal cells Differential ability of tumour and normal cells
to repair radiation damageto repair radiation damage
Brachytherapy
TeletherapyTeletherapy
Treatment: RadiotherapyTreatment: Radiotherapy
Long-Term ComplicationsLong-Term Complications– Most related to long-term microvascular Most related to long-term microvascular
changeschanges– Radiation pneumonitis/pulmonary Radiation pneumonitis/pulmonary
fibrosis fibrosis – Demyelination/memory Demyelination/memory
changes/dementiachanges/dementia– InfertilityInfertility– Second cancersSecond cancers
Treatment: Systemic Treatment: Systemic TherapyTherapy
ChemotherapyChemotherapy Hormonal TherapyHormonal Therapy ImmunotherapyImmunotherapy Small molecules/monoclonal Small molecules/monoclonal
antibodiesantibodies
Treatment: ChemotherapyTreatment: Chemotherapy
Based on the (now disproved) notion Based on the (now disproved) notion that cancer cells divide more rapidly that cancer cells divide more rapidly than normal cellsthan normal cells
Chemotherapy drugs tend to Chemotherapy drugs tend to interfere with a cell’s ability to divide interfere with a cell’s ability to divide normallynormally
Cells which cannot divide normally Cells which cannot divide normally should undergo apoptosisshould undergo apoptosis
Treatment: ChemotherapyTreatment: Chemotherapy
Mechanisms of actionMechanisms of action– Bind to DNABind to DNA
Alkylating agents, platinum agentsAlkylating agents, platinum agents
– AntimetabolitesAntimetabolites 5-FU, methotrexate5-FU, methotrexate
– Bind to microtubulesBind to microtubules Vinka alkylaoids, taxanesVinka alkylaoids, taxanes
– Interfere with topoisomeraseInterfere with topoisomerase AnthracyclinesAnthracyclines
Treatment: ChemotherapyTreatment: Chemotherapy
Acute toxicitiesAcute toxicities– Mucositis/diarrheaMucositis/diarrhea– NauseaNausea– Hair lossHair loss– MyelosuppressionMyelosuppression
Risk of febrile neutropeniaRisk of febrile neutropenia
Treatment: ChemotherapyTreatment: Chemotherapy
Chronic ToxicitiesChronic Toxicities– InfertilityInfertility
Particularly alkylating agentsParticularly alkylating agents
– LeukemogenesisLeukemogenesis Anthracyclines, alkylating agentsAnthracyclines, alkylating agents
– NeurotoxicityNeurotoxicity Cisplatin, taxanes, vinca alkyloidsCisplatin, taxanes, vinca alkyloids
– NephrotoxicityNephrotoxicity CisplatinCisplatin
Treatment: Hormonal Treatment: Hormonal TherapyTherapy
Hormone sensitive cancersHormone sensitive cancers– BreastBreast– ProstateProstate– EndometrialEndometrial– OvarianOvarian
Tumours retain some characteristics Tumours retain some characteristics of the original tissueof the original tissue
Treatment: Monoclonal Treatment: Monoclonal AntibodiesAntibodies
Antibody Target Tumour
Trastuzumab (Herceptin) HER-2 BreastRituximab (Rituxan) CD-20 LymphomaCetuximab (Erbitux) EGFR ColonBevacizumab (Avastin) VEGF Colon, LungTositumomab (Bexxar) CD-20 + I131 LymphomaIbritumomab (Zevalin) CD20 + Y Lymphoma
Treatment: Small MoleculesTreatment: Small Molecules
Molecules developed to inhibit Molecules developed to inhibit specific proteins/enzymes specific proteins/enzymes responsible for malignant behaviorresponsible for malignant behavior– Imatinib (Glivec)Imatinib (Glivec) CML, GISTCML, GIST– Gefitinib (Iressa)Gefitinib (Iressa) Lung cancerLung cancer– Erlotinib (Tarceva)Erlotinib (Tarceva) Lung cancerLung cancer
Lung CancerLung Cancer
Divided into:Divided into:– Non-small cell – 80%Non-small cell – 80%
AdenocarcinomaAdenocarcinoma– Bronchoalveolar carcinomaBronchoalveolar carcinoma
SquamousSquamous Large CellLarge Cell
– Small cell – 20%Small cell – 20%
Lung Cancer: NSCLCLung Cancer: NSCLC
Typically staged by CT thorax, abdo, Typically staged by CT thorax, abdo, head, bone scan, and mediastinoscopy if head, bone scan, and mediastinoscopy if surgery is consideredsurgery is considered
Stage I-II diseaseStage I-II disease– Limited to lung and ipsilateral hilar nodesLimited to lung and ipsilateral hilar nodes– Surgery gives ~50% long-term survival rateSurgery gives ~50% long-term survival rate– Improved to ~60-65% with adjuvant Improved to ~60-65% with adjuvant
chemotherapychemotherapy
Lung Cancer: NSCLCLung Cancer: NSCLC
Stage III DiseaseStage III Disease– Lung and ipsilateral or contralateral Lung and ipsilateral or contralateral
mediastinal lymph nodesmediastinal lymph nodes– Seldom amenable to surgerySeldom amenable to surgery– Radiation alone can cure 7-12%Radiation alone can cure 7-12%– Adding chemotherapy increases rate to Adding chemotherapy increases rate to
~18%~18%– Treatment can be difficult, and many Treatment can be difficult, and many
patients are not candidatespatients are not candidates
Lung Cancer: NSCLCLung Cancer: NSCLC
Stage IVStage IV– Metastatic diseaseMetastatic disease– Incurable, with median untreated Incurable, with median untreated
survivals of 4 monthssurvivals of 4 months– With chemotherapy, median survival With chemotherapy, median survival
increases to 8 monthsincreases to 8 months– 50% of patients have improved 50% of patients have improved
symptoms or QoL on chemosymptoms or QoL on chemo
Lung Cancer: Small CellLung Cancer: Small Cell
Staged as either Limited or ExtensiveStaged as either Limited or Extensive– LimitedLimited
Confined to one hemithoraxConfined to one hemithorax Treated with chemo and radiation, with a Treated with chemo and radiation, with a
long-term survival rate of ~25%long-term survival rate of ~25% Median survival untreated: 4 months Median survival untreated: 4 months
treated: 12 monthstreated: 12 months
Lung Cancer: SCLCLung Cancer: SCLC
– ExtensiveExtensive Beyond one hemithoraxBeyond one hemithorax Treated palliatively with chemotherapyTreated palliatively with chemotherapy Median untreated survival 6 weeksMedian untreated survival 6 weeks Median treated survival 9 monthsMedian treated survival 9 months
Breast CancerBreast Cancer
In many ways, treatment by stage is In many ways, treatment by stage is similar to lung cancer:similar to lung cancer:– Stage I-II Stage I-II
Limited to breast and axillary lymph nodesLimited to breast and axillary lymph nodes Surgery alone cures 40-90%Surgery alone cures 40-90% Adjuvant chemotherapy or hormonal Adjuvant chemotherapy or hormonal
therapy reduces relative risk of relapse by therapy reduces relative risk of relapse by ~30%~30%
Adjuvant radiation reduces risk of local Adjuvant radiation reduces risk of local relapse after breast-conserving surgeryrelapse after breast-conserving surgery
Breast CancerBreast Cancer
Stage IIIStage III– Locally advanced disease, often not Locally advanced disease, often not
amenable to surgery initiallyamenable to surgery initially– Many respond to neoadjuvant Many respond to neoadjuvant
chemotherapy, and go on to surgerychemotherapy, and go on to surgery Stage IVStage IV
– Palliative, with hormones, chemotherapy, Palliative, with hormones, chemotherapy, monoclonal antibodies, radiation as monoclonal antibodies, radiation as indicatedindicated
– Median survival ~1.5 years, but lots of Median survival ~1.5 years, but lots of variationvariation
Colon CancerColon Cancer
Staged by CT abdo, chest X-ray, bone Staged by CT abdo, chest X-ray, bone and brain scan if rectal, rather than and brain scan if rectal, rather than coloncolon
Stage I-IIIStage I-III– Typically treated by surgery, with long-term Typically treated by surgery, with long-term
control rates of 40-85%, depending on stagecontrol rates of 40-85%, depending on stage– Adjuvant chemotherapy decreases relative Adjuvant chemotherapy decreases relative
risk of recurrence by 30%risk of recurrence by 30%– Adjuvant chemo and radiation often used Adjuvant chemo and radiation often used
together in rectal, rather than colon cancerstogether in rectal, rather than colon cancers
Colon CancerColon Cancer
Stage IVStage IV– Palliated by chemotherapy, radiation as Palliated by chemotherapy, radiation as
indicatedindicated– Untreated survival ~4-6 monthsUntreated survival ~4-6 months– Optimally treated survival ~24 monthsOptimally treated survival ~24 months
Prostate CancerProstate Cancer
Treatment determined in large part Treatment determined in large part by grade of tumour, and age of by grade of tumour, and age of patient, in addition to stagepatient, in addition to stage
There is controversy about treatment There is controversy about treatment at virtually all stages of diseaseat virtually all stages of disease
For cancer limited to the prostate, For cancer limited to the prostate, the controversy is between radical the controversy is between radical radiation and surgical resection radiation and surgical resection
Prostate CancerProstate Cancer
More advanced disease is treated More advanced disease is treated with some combination of radiation with some combination of radiation and hormone therapy (androgen and hormone therapy (androgen deprivation)deprivation)
Chemotherapy has a limited role, Chemotherapy has a limited role, usually just for metastatic disease usually just for metastatic disease after hormones failafter hormones fail