Oncology seminar

Oncology Dr Shemsu.s

April 2013

Wednesday, April 12, 2023 Oncology

Out line of Presentation

• Introduction• Epidemiology• Cancer Etiology• Cancer Biology• Cancer Risk Assessment• Cancer Screening• Diagnosis• Staging• Surgical Approach to Cancer Therapy• Chemotherapy • Radiation Therapy


INTRODUCTION

• Tumor - “abnormal mass of tissues the growth of which exceeds and is uncontrolled with that of normal tissues” Wills

• Cancer – ”Karanikos”


Epidemiology

• In 2008 - 1.44 million new cases in US.• 565,650 – died in US

• Global Statistics on Cancer Incidence -10.9 million new cancer cases in 2002. -Lung cancer is the leading cancer in the world. - Breast cancer - the second most common


Cancer Etiology

• Genetic disease• Somatic mutation• Germ line mutation• Hereditary cancer


• factors may suggest hereditary cancer 1. Tumor development at a much younger age than

usual 2. Presence of bilateral disease 3. Presence of multiple primary malignancies 4. Presentation of a cancer in the less affected sex 5. Clustering of the same cancer type in relatives 6. Occurrence of cancer in association with other

conditions such as mental retardation or pathognomonic skin lesions


• Importance of knowing hereditary cancer

– Examples• P53 and li-fraumani syndrome• RB1 Gene and Hereditary Retinoblastoma• BRCA1, BRCA2, and Hereditary Breast-Ovarian

Cancer Syndrome• APC Gene and Familial Adenomatous Polyposis


Carcinogens

• Environmental factors - 60 to 90% • Three types - Chemical, Physical, or Viral

• Chemicals carcinogens • Three groups 1.genotoxins . 2. co carcinogens-potentiate genotoxins. 3.Tumor promoters.• IARC - 4 Groups• E.g. of Proven carcinogens -

aflatoxins ,tobaco ,aresnic ,benzene etc


Physical Carcinogen

• Mechanism - Induction of inflammation and cell proliferation - Induce DNA damage• Radiation - Best known physical carcinogen• Ionizing -DNA break( deletion ,gene rearrangement -Direct effect -Indirect effect -Bystander effect• Non-ionizing -UV light-skin cancer


Viral Carcinogens

• 15 % cancers world wide• Mechanism -Insertional mutagenesis -Expression of oncogenes -Alteration of immune system• DNA virus -Have their own Oncogen -Oncoprotiens –bind cellular genes-p53.RB -activate cellular genes-IL-5,C—MYC,H-ras -E.g.- HPV, HBV, EBV


• RNA virus - Are retroiviruses -They have no their own oncogenes -Transform host proto oncogene E.G-HTLV-1


Cancer Biology


TUMORIOGENESIS

• Phenotipicaly • Genetically• Initiation• A single cell or clone• Field effect• Promotion• Progression– From benign lesion to CIN to invasive lesion– Accumulate genetic changes


Tumor growth


Major Classes of Genes Altered

• Oncogen• Tumor suppressor gene• Proapoptotic genes• Oncogenes -Proto-oncogenes →oncogenes -Three letter abbr - e.g. myc ,ras, prefix v or c

-Can be activated by translocation (e.g., abl), -Promoter insertion e.g., c-myc, -Mutation - e.g., ras, -Amplification (e.g., HER-2/ neu).


Function of Oncogenes

• Promote growth– Growth factors- PDGF, FBGF.– GF receptors- e.g., HER2, HER1

• Intracellular signal transduction molecules (e.g., ras).• Nuclear transcription factors e.g., c-myc.


Tumor Suppressor Genes

• p53, pRB.• APC• TGF-B• Function -Arrest cell cycle -Induce apoptosis -Activate other genes


Evasion of Apoptosis

• Two path ways -Death receptor path way - Fas(CD95) -The mitochondrial Path wayStimulus - DNA damage, free radicals, withdrawal of GFs

• E.g. – Loss of CD 95 In HCC


Cancer Invasion

• Carcinoma insitu• Invasive cancer• Steps -Loss of adhesion – cadherins -Attachemement to ECM -Degradation of ECM -locomotion


ANGIOGENESIS

• Proangiogenic factors- VEGF, FGF• Antiangiogenic factors- Thrombospondin 1,

Angiostatin

• Source –tumor cells-RAS,myc,HER2/NEU ,endothelial cells ,Inflammatory cellsEffect - nutrition, metastasis -Remval of Primary Tumor


Metastasis

• Hematogenous • lymphatic• seeding in to body cavities.

Prerequisites -Access to circulation -survive in the circulation. -Extravasate -Initiate growth in the new tissuesOrgan specific metastasis - mechanical -Seed and soil theoryDormancy.


Cancer Risk Assessment

• Initial evaluation of any patient• Cancer screening - genetic counseling and testing• Component -Complete history -Hx of environmental exposure -Detailed family history -Personal history -Age, race - E.g.-GAIL model for breast cancer


Cancer Screenings

Early detection Criteria for screening

• The Disease -Recognizable early stage -Treatment at an early stage more effective than at a later

Stage -Prevalence


• The Test - Sensitive and specific -Acceptable to the screened population -Safe -Inexpensive

• The Programme• Intensive screening


Cancer Diagnosis

• The Definitive - Biopsy of the lesion - histology, grade• Open biopsy -Inscisional or Excisional -More tissue for histologic Dx• CORE Biopsy• FNAC


Staging

• Anatomic extent of tumor in an individual patients• Importance - To predict prognosis - Selection of Therapy -Evaluation of Treatment -Exchange of information among Treatment

centers


• TNM Staging

- Before definitive therapy

- 4 month

- Microscopically confirmed Cancer - cTNM , pTNM, aTNM, rTNM - Multiple Tumors - T2(5), T2(m) - Unknown Primary - Paired Organs - Stage Grouping


• cTNM Primary tumor(T) -P/E , Imaging studies, Endoscopy -Size ,Extent, Multiplicity - Tx, T0, T is - T1, T2 , T3

• Regional LN ( N ) -Based on size -Characteristics, and location. -NX ,N0 - N1 ,N2 , N3

• M - distant metastasis - clinical examination

- M0 , M x


Surgical Approach to Cancer Therapy

• Prevention• Diagnosis• Staging• Treatment• Palliation• Rehabilitation• Surgeons Role


• Management of Primary Tumor -Goal of surgical mx- oncologic cure -Operable - negative surgical margin - Inoperable - positive surgical margin

• Radical vs conservative management

• Appropriate surgical margin


Breast Cancer

Oncology

Surgical Management of the Regional Lymph Node Basin

• Cancers• Soft tissue sarcomas • Methods -Enbloc Removal of Primary Tumor With the LN - Separate Incision• Advantage Clinically Negative Node• Lymphatic mapping and Sentinnel LN Biopsy - Identification Rate - False Negative Rate - AdvantageWednesday, April 12, 2023


Surgical Management of Distant Metastases

• Mostly non curative • Curable in isolated metastasis• Survival rates depends on - Disease free interval - Natural history o f metastatic disease

• The goal is to resect the metastases with negative margins


Principles of Chemotherapy

• Fractional cell kill - Constant percentage of cells killed - E.g. 1012 tumor cells, treated with a dose that result in

3 log kill 1012 → 109 cells

• Selection of chemotherapeutic agent• Conventional dose• High dose • Cyclic Therapy


• End Point of Drug Action - Metastatic Disease - Localized Tumors - Adjuvant Therapy -Sensitizes Tumors to radiation -As part of adjuvant therapy -Palliative therapy

• Classification -Cell-cycle phase–nonspecific agents -Cell-cycle phase–nonspecific agents


• AgentsAlkylating agents - Kill cells in any phase of the cycle - MOA : cross linking the DNA strands and direct damage to

the DNA

- Three Groups –Classic ,, miscellaneous DNA Binding Agents - Classic - Cylophosphamide, Busulfan , Chlorambucil - Nitrosureas- Streptozocin ,Carmustine - miscellaneous- cisplatin, Carboplatin - Toxicity :


Antimetabolites - cell-cycle–specific agents - Effective in tumors with high growth fraction -MOA : analogues of naturally occuring

metabolities involved in DNA synthesis

-Eg. - Folic acid Analogue - Methotrexate , - Pyrimidine Analogue- 5-FU - Purine Analogue - Azathioprine , Mercaptopurine

-Toxicity:


• Plant Alkaloids - Derived from vinca rosea plant - Act by binding to tubulin in the S phase - Eg. - Vincristin, vinblastin - Toxicity:

• Combination therapy: - Maximizes Cell kill -Broader Range of Coverage of Resistant cell lines -Delays the emergence of Drug-Resistant cell lines


Response evaluation

-Complete response -Partial response -Minimal response -Progressive disease


Radiation Therapy

• Ectro magnetic Waves -Penetrate Tissues Deep• Particulate - electrons, superficial lesion

• Biologic bases -DNA breaks, cross linking - Indirectly ionizing - X-ray ,Gamma rays - Directly ionizing - Electrons, Neutrons

• Factors Influence Cell Killing -Tissue Factor - Physical Parameter of Radiation


Factors influence cell killing


• Radiation sentisizers - Metronidazole , misonidazole - Thymidine analogue - iododeoxy uridine. - 5 FU, actinomicin D


• Planning therapy -Define Target - Shield -Homologues delivery -Fraction Dose• Conventional fractionation - 1.8-2 Gy/d,5 day /wk for 3-7

wks

• Ways of delivery -Tele Therapy -Brachy Therapy -Systemic Therapy

• Preop or post op


• Indication - Component of Curative Therapy -Palliation - Prevent Development of Disease

• Toxicity- Acute and Chronic


• Other Option of Therapy - Hormonal - Targeted Therapy - Gene Therapy


REFFERENCE

• SCWARTZ PRINCIPLES OF SURGERY• ROBINS PHOLOGIC BASES OF DISEASE• INTERNET

THNK YOU

Oncology seminar

Health & Medicine

Transcript of Oncology seminar