Oncology Basics CANCER TREATMENT MODALITIES - PowerPoint Presentation

1. Oncology BasicsCANCER TREATMENT MODALITIESMohammed A. Suwaid, MDBoard-certified Medical OncologistAnbar Cancer Center

2. AGENDACancer OncologyRole of MDT in managing cancerSurgical treatmentRadiation treatmentSystemic treatment

3. WHAT IS CANCERUncontrolled (abnormal excessive uncoordinated autonomous and purposeless) proliferation of cells.NEOPLASMCANCERUncontrolled proliferation and spread within the body of abnormal forms of body's own cells.

4. IS CANCER MANAGEABLE?IS CANCER CURABLE?The most significant 5 year survival is achieved in patients with skin, thyroid, cervix, uterus and bladder cancers.The worst survival is with pancreatic cancer.Females tend to have better numbers of 5 year survival than males, for ??

5. ONCOLOGYSystemic Rx for solid tumors, hematological malignancies and HSCT.MEDICALoncologyCLINICAL oncologySystemic Rx for solid tumorsRTH for solid and hematological malignancies SURGICAL oncologySurgical removal of cancerRADIATION oncologyRTH for solid and hematological malignancies NUCLEAR medicineRadioactive substancesONCOS = TUMORLOGOS = STUDY

6. MULTIDISCIPLINARY TEAMTUMOR BOARDIntegrated team approach to medical care in which cancer professionals consider all relevant treatment options and develop an individual treatment PLAN for each patient collaborativelyFighting the Crab – Kiev, Ukraine

7. MULTIDISCIPLINARY TEAMMEDICALoncologistCLINICAL oncologistSURGICAL oncologistRADIATION oncologistNUCLEAR physicianPATHOLOGISTDIETICIANRADIOLOGISTINTERNISTOTHERSRehab., psych., etc.MDT

8. CASE SCENARIOA 30-year-old lady presented to the GP with a breast lump associated with redness and ulceration of the overlying skin. He sent her for US which revealed a 5cm highly suspicious mass (BIRADS V) with few enlarged axillary LNs. FNAC revealed malignant cells. Which is the best option for managing this patient? A. Surgical removal of the mass and LNs.B. Radiotherapy to the breast and axilla.C. Chemotherapy plus hormonal treatment.D. Discussion within a context of MDT.BIRADS: Breast Imaging-Reporting and Data System

9. CASE SCENARIOA. Surgical removal of the mass and LNs.B. Radiotherapy to the breast and axilla.C. Chemotherapy plus hormonal treatment.D. Discussion within a context of MDT.A 30-year-old lady presented to the GP with a breast lump associated with redness and ulceration of the overlying skin. He sent her for US which revealed a 5cm highly suspicious mass (BIRADS V) with few enlarged axillary LNs. FNAC revealed malignant cells. Which is the best option for managing this patient? BIRADS: Breast Imaging-Reporting and Data System

10. TREATMENT MODALITIESProphylactic treatmentTreatment of establishes casesSurgeryRadiotherapySystemic therapyWithin a context of MDT

11. PROPHYLACTIC TREATMENTSurgical removal of a well known precancerous lesion.Examples:FAP  total proctocolectomy.BRCA-1/BRCA-2  bilateral mastectomy and prosthesis.FAP: Familial adenomatous polyposisBRCA: Breast cancer gene

12. TREATMENT OF ESTABLISHED CASESRequires MDTDepends on tumor grading, staging and other factors.Two major categories (goals):Curative  early (locoregional) potentially operable disease. Surgery ± radiotherapy ± systemic therapyPalliative  late (metastatic) incurable and inoperable disease. Systemic Rx, usually no place for surgery or RTH (with exceptions).

13. TREATMENT OF ESTABLISHED CASESCriteria of incurability:Distant metastasis(es)  most commonExtensive locoregional disease with infiltration of adjacent organsPerformance statusComorbidities

14. SURGERY

15. TYPES OF SURGERYWide local excision e.g. early breast cancer, skin BCCRadical local excision e.g. Breast cancer + LN, CRC stage III Metastasectomy e.g. met CRCCURATIVEPALLIATIVESymptomatic RxQoLE.g. gastrojejunostomy, toilet mastectomy

16. SURGERYA 50-year-old female referred to you from the GP with a recent history of anemia and +ve FoB. You requested colonoscopy which revealed polypoidal growth involving the sigmoid . Histopathology  Grade II adenocarcinoma. Imaging  -ve LN, -ve met.The patient has good PS and has no significant comorbidities.What is the best next step according to MDT discussion?SurgeryRadiotherapyChemotherapyPalliative treatment

17. SURGERYA 50-year-old female referred to you from the GP with a recent history of anemia and +ve FoB. You requested colonoscopy which revealed polypoidal growth involving the sigmoid . Histopathology  Grade II adenocarcinoma with LVI. Imaging  +ve LN, -ve met.~ 15 kg lost in the last 6mo, good PS, no significant comorbidities.What is the best next step according to MDT discussion?SurgeryRadiotherapyChemotherapyPalliative treatment

18. RADIOTHERAPY

19. RADIOTHERAPYUses ionizing radiation to treat cancerSources of IR:Natural: radioactive decay of Uranium, Plutonium, Cobalt, Radium, Iodide, etc.Man-made: LINAC system, Cyclotrons by sudden deceleration of high speed electrons when hitting a tungsten targetTungsten target implies an X-Ray tube where high energy electrons are directed in a vacuum to strike a tungsten target.

20. BIOLOGICAL EFFECTS OF RTHRTH causes ionization in tissuesThis causes formation of free radicalsFR interact and damage DNADamaged DNA is unable to replicate during mitosisCELL DEATH

21. ROLE OF RTHAbout 50 % of cancers will require RTH2/3 of the cases uses RTH with curative intentH&N CervixAnalSkinProstateBladderEarly lungEarly esophagusSeminomaHL & NHLMedulloblastomas and certain Brain tumors

22. TYPES OF RTH INTERVENTIONSPre-operative RTHAdvantages:Downsize tumorLess mutilating SxSterilize SMDisadvantages:Clinical stagingOvertreatment May ↑ Sx morbidity if radioresistant Ca

23. TYPES OF RTH INTERVENTIONSPost-operative RTHAdvantages:Pathological stagingNo overtreatmentDisadvantages:Larger RTH field to cover the surgical bedPoorer blood supply  less effective↑ late morbidity

24. SYSTEMIC ANTI-CANCER TXChemotherapyTargeted therapyHormonal therapyImmunotherapy

25. CHEMOTHERAPYWhy term chemotherapy?Antimicrobial chemotherapySome malignant cells can be cultured…Some malignancies can be transmitted by inoculation…

26. CHEMOTHERAPYIs cancer chemotherapy as successful as antibiotic chemotherapy?NOMetabolism in bacteria differs qualitatively from host cells, while metabolism in cancer cells differ only quantitatively from normal host cells.

27. CHEMOTHERAPYHENCETarget selectivity is more difficult in cancerCancer cells do not cause a substantial immune responseDiagnostic complexity  delay in institution of treatment

28. CHEMOTHERAPYGuiding principles:Early diagnosis and early institution of treatmentTotal cell kill must be tried to achieve cureCombination chemotherapyIntermittent regimensAdjuvant and neoadjuvant chemotherapy

29. EARLY DX AND EARLY TXWhy?Survival time inversely related to initial number of cellsAging cancer cells are less susceptible to chemotherapy, because:↑ cell cycle (division) time↓ actively dividing cells with more resting cellsOvercrowding of cells

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31. TOTAL CELL KILLAimed at destroying all malignant cells leaving none.This approach ensures:Early recoveryPrevent relapsesProlongs survival

32. KINETIC BASIS OF DRUG THERAPYThe objective of cancer treatment is to reduce the tumor cell population to zero cells.Fractional cell kill hypothesis states that a given drug concentration applied for a defined time period will kill a constant fraction of the cell population, independent of the absolute number of cells.Thus, each treatment cycle kills a specific fraction of the remaining cells. The results of treatment are a direct function of :(a) The dose of drug administered.(b) The number and frequency of repetition of treatment.

33. TOTAL CELL KILLAimed at destroying all malignant cells leaving none.This approach ensures:Early recoveryPrevent relapsesProlongs survival

34. COMBINATION CTHHeterogenicity of cells remaining in different phases of cell cycle, showing different levels of sensitivityDifferent biochemical sites of actionAvoid emergence of drug resistanceWith rare exceptions, single drugs in standard doses do not cure cancer. Monotherapy is adequate in Burkitts lymphoma & choriocarcinoma

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36. INTERMITTENT REGIMENSRisk-benefit ratioTime for normal host cells to recoverKill cancer…save the patient…

37. ADJUVANT & NEOADJUVANTAdjuvant chemotherapy:Chemotherapy given after surgery or irradiation to destroy micrometastasis & prevent development of secondary neoplasm.Neo-adjuvant chemotherapy:Chemotherapy given before surgery or radiotherapy in order to diminish the volume of large primary neoplasm

38. INDIVIDUALIZING TREATMENT CHOICEChoice depends on:Histology, molecular and immunologic subtype, stage , and an additional factors, the patients probable tolerance for the side effects of various possible treatments.Severely debilitated patients and those with underlying medical problems, for example, renal failure, diabetes or chronic obstructive pulmonary disease might well suffer severely disabling or fatal complications from potentially curative regimens .When cure is not a realistic expectation, a decision to treat must be based on an expectation for prolongation of the patients life or an improvement in the quality of life. In these cases, treatment-related side effects may be minimized by dosage adjustments or treatment delays, when necessary, but at the cost of antitumor efficacy.

39. CLASSIFICATION OF CYTOTOXICSAlkylating agentsAntimetabolitesPlant alkaloids(Mitotic inhibitors) AntibioticsOthersNitrogen mustardsMelphalanCyclophosphamideIfosfamideChlorambucilAziridine (Ethylenimines)ThiotepaAlkyl sulfonate1. BusulfanNitrosoureasCarmustine (BCNU)Lomustine (CCNU)StreptozocinPlatinum compoundsCisplatinCarboplatinOxaliplatinHydrazine and Triazine DerivativesDacarbazine (DTIC)ProcarbazineTemozolomideNonclassic alkylatorsAltretamine Folate analogsMethotrexateTrimetrexatePemetrexedRaltitrexed Purine analogsFludarabine6-MP6-TGAdenosine analogsCladribinePentostatinPyrimidine analogs5-FUCapecitabineGemcitabineFloxuridine (5-FUdr)CytarabineSubstituted ureaHydroxyureaVinca alkaloidsVincristineVinblastineVindesine TaxanesPaclitaxelDocetaxelTopoisomerase inhibitors(Camptothecans, Topo I)Irinotecan TopotecanTopoisomerase inhibitors(Podophyllotoxins, Topo II)EtoposideTeniposideAnthracyclinesDoxorubicinDaunorubicinEpirubicinIdarubicinOther antibioticsDactinomycinBleomycinPlicamycinMitomycin-CMitoxantroneL-asparaginase

40. GENERAL TOXICITY OF CYTOTOXIC DRUGS • Nausea & Vomiting• Bone marrow depression• Alopecia• Gonads: Oligospermia, impotence, ↓ ovulation• Fetus: Abortion, fetal death, teratogenicity• Carcinogenicity• Hyperuricemia• Immunosupression: Fludarabine• Hazards to staff

41. SPECIFIC DRUG SIDE EFFECTSCisplatin: nephrotoxicityIfosfamide: hemorrhagic cystitisFludarabine: immunosuppressionIrinotecan: diarrheaDoxorubicin: cardiomyopathyTaxanes: SIADHOxaliplatin: NeuropathyBleomycin: pulmonary fibrosis

42. TARGETED CANCER THERAPY DEFINITIONTargeted drug is a drug that targets a specific molecule or pathway that plays a role in the growth and development of cancer rather than by simply interfering with all rapidly dividing cells. The goal of targeted drug therapy is to fight cancer with more precision and fewer side effects.

43. TARGETED CANCER THERAPYCLASSIFICATIONI. Monoclonal antibodiesThey are monospecific antibodies that target specific antigens found on the cell surface, such as transmembrane receptors or extracellular growth factors. This can lead to apoptosis, antibody-dependent cellular cytotoxicity, or complement-mediated cell lysis. Examples: Trastuzumab for the treatment of HER2/neu-positive breast cancer.Rituximab for the treatment of CD20+ B-cell NHL.

44. II. Small molecules:Tyrosine kinase receptor inhibitors: EGFR inhibitor e.g. Gefitinib for treatment of non-small cell lung cancer.PDGFR inhibitor e.g. Imatinib for Ph+ CML & ALL and KIT+ GISTVEGFR inhibitor e.g. Sunitinib for treatment of renal cell carcinomaProteasome inhibitors: e.g. Bortezomib for treatment of multiple myeloma.Cyclin-dependent kinase inhibitor: e.g. celiciclib which is now in multiple phase II studies for advanced NSCLC.TARGETED CANCER THERAPYCLASSIFICATION

45. III. Gene TherapyIs a technique used for correction of defective genes responsible for cancer development by incorporating specific ribonucleotide sequences into them. This is accomplished by a number of ways such as:Antisense therapy (RNA). Viral vector transfection (RNA or DNA).DNA injection into tumors.Ex vivo transfection of selected tumor cells, immune cells, or bone marrow progenitors (DNA).TARGETED CANCER THERAPYCLASSIFICATION

46. IV. Cancer vaccineIs a vaccine used to treat existing cancer or prevent the development of cancer in high-risk individuals by the use of tumor-specific antigens (and the immune response to them) for immune surveillance and tumor rejection.Several possibly effective cancer vaccines are currently in phase 3 trials.HPV vaccine for prevention of cervical cancer.TARGETED CANCER THERAPYCLASSIFICATION

47. HORMONAL THERAPYDEFINITION AND TYPESHormonal Therapy:Slow or stop the proliferation of cancer cells that are dependent on hormonal action to grow.Major types of hormonal therapy:Hormone-releasing factorsHormonesAntihormonesSelective Estrogen Receptor Modulators (SERM’s)Aromatase Inhibitors

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