CELLULAR REGULATION

• Carcinogenesis


  Malignant transformation
• Carcinogenesis


  1. Initiation

  2. Promotion

  3. Progression
• Initiation


  Carcinogens cause DNA mutations
• Usually managed by repair mechanisms or apoptosis
• Carcinogenic Agents and Factors

  • Viruses
  • Bacteria
  • Physical agents
  • Chemical agents
  • Genetic, familial factors
  • Lifestyle factors: exposure related
  • Hormonal agents - Endogenous or exogenous exposure
• May be combo genetic, environmental and lifestyle
• Lifestyle factors: exposure related

  • Poor diet, alcohol, obesity, alcohol, lack of physical activity
• Hormonal agents - Endogenous or exogenous exposure

  • Diethylstilbestrol exposure (multiple generational)
  • Prolong exposure to endogenous estrogen
  • Early menarche, late menopause, nulliparity, childbirth after 30 y/o
  • Hormone replacement therapy (HRT)
• Prevention

  1. Primary prevention with health promotion and risk reduction

  2. Secondary prevention with screening and early detection activities

  3. Tertiary prevention is monitoring for and prevention of recurrence of the primary cancer and development of secondary malignancies
• Primary prevention with health promotion and risk reduction

  • Maintain healthy weight, active lifestyle, healthy diet, limit alcohol, immunizations
• Secondary prevention with screening and early detection activities

  • Breast: Clinical breast exam, mammogram
  • Cervix: Pap smears
  • Colorectal: stool DNA, colonoscopy
  • Lung: Low dose CT scan if current/previous smoker
  • Prostate: Prostate-specific antigen test
• Tumor Staging

  Describes size, existence of local invasion, lymph node involvement, distant metastasis
• Tumor Grading

  Provides classification of differentiated (better prognosis) vs un-differentiated (poorer prognosis)
• Anatomic stage group, continuity in communication, treatment, prognosis, comparing outcomes
• Treatment options

  • Surgery, radiation, chemotherapy, hematopoietic stem cell transplant (HSCT), immunotherapy, targeted therapy
• Treatment goals

  • Cure – complete eradication of malignant disease
  • Control – prolonged survival and containment
  • Palliation – relief of symptoms, improvement of quality of life
• Treatment options and prognosis vary based on stage, grade, individual health status
• Treatment not started until diagnosis, stage and grade confirmed
• Multiple approaches used together or at different times during treatment
• Radiation Therapy

  • Curative: to definitively treat cancer
  • Control: when tumor cannot be removed, local node metastasis
  • Neoadjuvant: reduce tumor size prior to surgery
  • Prophylactically: prevent local recurrence or spread
  • Palliative: relieve symptoms, treat oncologic emergency
• Ionizing Radiation

  • Breaks the DNA strand leading to cell death
  • Indirect damage via free radicals
  • Immediately or apoptosis
  • Localized within treatment field
• Radiosensitive tissues

  • Bone marrow, lymphatic tissue, epithelium, GI tract, hair follicles, and gonads
• Radiosensitive tumor can be destroyed and still allow for repair of surrounding tissue</b>
• Smaller, highly proliferative and poorly differentiated tumors are more radiosensitive
• Radiation Dose

  • Sensitivity of target tissue
  • Size
  • Radiation tolerance of normal tissue
  • Structures adjacent to the tumor
  • Lethal tumor dose: the dose that will eradicate 95% of tumor while preserving normal tissue
• Radiation Administration

  • External Radiation: External-beam radiation therapy (EBRT)
  • Internal Radiation: Brachytherapy, Interstitial implants, Intracavitary radioisotopes, Systemic radiotherapy
• Radiation Toxicity

  • Altered skin integrity, Alopecia, Radiodermatitis
  • Altered oral mucosa
  • Systemic side effects: Fatigue, malaise, and anorexia
  • Late effects: Chronic and permanent, Lower incidence due to advances in treatment planning
• Toxicity can cause interruption, delay or cessation of radiation therapy
• Re-epithelialization occurs after radiation therapy is complete
• Hyperpigmentation occurs 2-4 weeks after initiation of radiation therapy
• Chemotherapy

  • Drugs used in attempt to destroy cancer cells by interfering with cellular functions such as replication and DNA repair
  • Used in systemic disease, neoadjuvant therapy, adjuvant therapy, leukemia or lymphoma
  • Goals: Curative, control, or palliative
• Chemotherapy is based on cell cycle and repeated doses over a prolonged period
• 20-99% of tumor cells are destroyed with each chemotherapy exposure
• The goal is to eradicate enough tumor to allow the immune system to manage the remaining
• Chemotherapy Classification

  • Mechanism of action to cell cycle
  • Chemical group
  • Administration: Inpatient, Outpatient, Home setting
  • Multiple routes
  • Type of agent
  • Required dose
• Chemotherapy Dosage

  • Determined for maximal cell kill with minimal impact on healthy tissue
  • Factors: Total body surface area, Patients weight, Previous exposure and response to chemotherapy/radiation, Function of major organ systems
• Chemotherapy Complications

  • Extravasation: infiltration of drug
  • Hypersensitivity: 5 min- 6 hours
  • Toxicity: Acute or chronic
• Chemotherapy Toxicity

  • Gastrointestinal
  • Hematopoietic -> Myelosuppression
  • Renal
  • Cardiopulmonary
  • Reproductive
  • Neurologic
• Gastrointestinal Toxicity

  • N/V may persist 24-48 hours; delayed N/V up to 1 week after tx
  • Affects QOL, psychological status, nutrition, F&E status, functional ability, compliance, and increased utilization of resources
• Hematopoietic Toxicity

  • Leukopenia, neutropenia, anemia, thrombocytopenia
  • Increased risk of infection and bleeding