Chapter 11: Oncology Flashcards
2 cause of death in the United States
Cancer
MC Ca in women
Breast cancer
MCC cancer related death in women
Lung cancer
MC Cancer in men
Prostate cancer
Used to identify metastases; defects fluorodeoxyglucose molecules
PET (positron emission tomography)
Need MHC complex to attack tumor
Cytotoxic T cells
Can independently attack tumor cells
Natural killer cells
Are random unless viral-induced tumor
Tumor antigens
Tumor marker: colon ca
CEA
Tumor marker: liver CA
AFP
Tumor marker: pancreatic CA
CA 19-9
Tumor marker: Ovarian ca
CA 125
Tumor marker: testicular Ca, choriocarcinoma
Beta-HCG
Tumor marker: prostate CA
PSA
Prostate CA: thought to be tumor marker with the highest sensitivity, although specificity is low
PSA
Tumor marker: small cell lung CA, neuroblastoma
NSE
Tumor marker: breast CA
BRCA I and II
Tumor marker: carcinoid tumor
Chromogranin A
Tumor marker: thyroid medullary CA
Ret oncogene
Half life: CEA
18 days
Half life: PSA
18 days
Half life: AFP
5 days
Two components of cancer transformation
- Heritable alteration in genome and;
2. Loss of growth regulation
Oncogenesis: time between exposure and formation of clinically detectable tumor
Latency period
Three phases of latency period
- Initiation (carcinogen acts with DNA)
- Promotion (then occurs)
- Progression (cancers cells to clinically detectable tumor)
What can neoplasms arise from?
Carcinogenesis (e.g. smoking)
Viruses (eg, EBV)
Immunodeficiency (eg HIV)
What do retroviruses contain?
Oncogenes
Associated with Burkitt’s lymphoma (8:14 translocation) and nasopharyngeal CA (c-myc)
Ebstein-Barr Virus
Human genes with malignant potential
Proto-oncogenes
Infectious agent: cervical cancer
Human papillomavirus
Infectious agent: gastric cancer
Helicobacter pylori
Infectious agent: hepatocellular carcinoma
Hepatitis B and hepatitis C viruse
Infectious agent: nasopharyngeal carcinoma
EBV
Infectious agent: Burkitt’s lymphoma
EBV
Infectious agent: various lymphomas
HIV
Most vulnerable stage of cell cycle for XRT
M phase
Radiation therapy: what causes most of the damage?
Most damage done by formation of oxygen radicals -> maximal effect with high oxygen levels
Main target of radiation therapy
DNA: oxygen radicals and XRT itself damage DNA and other molecules
How does high-eneregy radiation have a skin–preserving effect?
Maximal ionizing potential not reached until deeper structures
What do fractionate XRT doses allow?
- Repair of normal cells
- Re-oxygenation of tumor
- Redistribution of tumor cells in the cell cycle
Very radiosensitive tumors
Seminomas, lymphomas
Very radio resistant tumors
Epithelial, sarcomas
Less responsive to XRT due to lack of oxygen in the tumor
Large tumors
Source of radiation in or next to tumor (Au-198, I-128); delivers high, concentrated doses of radiation
Brachytherapy
Chemo Agent: exhibit plateau in cell-killing ability
Cell cycle-specific agents (5FU, methotrexate)
Chemo Agent: Linear response to cell killing
Cell cycle-nonspecific agents
Chemo Agent: Decreases short-term (5 year) risk of breast CA 45%
Tamoxifen (blocks estrogen receptor)
Complications: tamoxifen therapy
1% risk of blood clots
0.1 % risk of endometrial cancer
Chemo Agent: promotes microtubule formation and stabilization that cannot be broken down; cells are ruptures
Taxol
Chemo Agent: can cause pulmonary fibrosis
Bleomycin
Busulfan
Chemo Agent: nephrotoxic, neurotoxic, ototoxic
Cisplatin (platinum alkylating agent)
Chemo Agent: bone (myelo) suppression
Carboplatin (platinum alkylating agent) and
Vinblastine (microtubule inhibitor)
Chemo Agent: peripheral neuropathy, neurotoxic
Vincristine (microtubule inhibitor)
Chemo Agent: transfer alkyl groups; forms covalent bonds to DNA
Alkylating agents
Chemo Agent: Acrolein is the active metabolite.
- Side effects: gonadal dysfunction, SIADH, hemorrhagic cystitis
Cyclophosphamide
Tx: hemorrhagic cystitis s/t cyclophosphamide
Mesna
Chemo Agent: antihelminthic drug though to stimulate immune system against cancer
Levamisole
Chemo Agent: inhibits dihydrofolate reductase (DHFR), which inhibits purine and DNA synthesis
- Side effects: renal toxicity, radiation recall
Methotrexate
Reverses effects of methotrexate by re-supplying folate
Leucovorin rescue (folinic acid)
Chemo Agent: inhibits thymidylate synthetase, which inhibits purine and DNA syntehsis
5-fluorouracil (5FU)
Increases toxicity of 5-fluorouracil
Leucovorin (folinic acid)
Chemo Agent: DNA intercalator, oxygen radical formation
Doxorubicin
Side effects: doxorubicin
Heart toxicity secondary to oxygen radicals at total doses > 500 mg/m^2.
Chemo Agent: inhibits topoisomerase (which normally unwinds DNA)
Etoposide (VP-16)
Chemo Agents: least myelosuppression
Bleomycin, vincristine, busulfan, cisplatin
Used for neutrophil recovery after chemo; side effects - Sweet’s syndrome (acute febrile neutropenic dermatitis)
GCSF (granulocyte colony-stimulating factor
Acute febrile neutropenic dermatitis
Sweet’s syndrome
When to consider resection of a normal organ to prevent cancer -> breast
BRCA I or II with strong family history
When to consider resection of a normal organ to prevent cancer -> thyroid
RET proto-oncogene with family history thyroid cancer
Tumor suppressor gene: chromosome 13; involved in cell cycle regulation
Retinoblastoma
Tumor suppressor gene: chromosome 17; involved in cell cycle
p53
Normal gene induces cell cycle arrest and apoptosis; abnormal gene allows unrestrained cell growth
p53
Tumor suppressor gene: chromosome 5, involved with cell cycle regulation and movement
APC
Tumor suppressor gene: chromosome 18; involved in cell adhesion
DCC
Tumor suppressor gene: involved in apoptosis (programmed cell death)
bcl
Chromosome: p53
17
Chromosome: APC
5
Chromosome: DCC
18
Proto-oncogene: G protein defect
ras proto-oncogene
Proto-oncogene: tyrosine kinase defect
src proto-oncogene
Proto-oncogene: platelet-derived growth factor receptor defect
sis proto-oncogene
Proto-oncogene: epidermal growth factor receptor defect
erb B proto-oncogene
Proto-oncogene: proto-oncogenes - transcription factors
myc (c-myc, n-myc, l-myc)
Defect in p53 gene -> patients get childhood sarcomas, breast CA, brain tumors, leukemia, adrenal CA
Li-Fraumeni syndrom
- Gene involved in development include APC, p53, DCC, and K-ras
- APC though to be initial step in evolution
- Does not usually go to bone
Colon cancer
Carcinogens: coal tar
Larynx, skin, bronchial CA
Carcinogens: beta-naphthylamine
Urinary tract CA (bladder CA)
Carcinogens: benzene
Leukemia
Carcinogens: asbestos
Mesothelioma
DDX: suspicious supraclavicular node
Neck, breast, lung, stomach (Virchow’s node), pancreas
DDX: suspicious axillary node
Lymphoma (#1), breast, melanoma
DDX: suspicious periumbilical node
Pancreas (Sister Mary Joseph’s node)
DDx: ovarian metastases
Breast (#1), prostate
DDx: skin metastases
Breast, melanoma
DDx: small bowel metastases
Melanoma (#1)
Clinical trials:
- Phase 1
- Phase 2
- Phase 3
- Phase 4
- Phase 1: Is it safe and at what dose?
- Phase 2: Is it effective?
- Phase 3: Is it better than existing therapy?
- Phase 4: implementation and marketing
What is induction therapy?
Sole treatment; use for advanced disease or when no other treatment exists
What is primary therapy?
(Neoadjuvant) - chemo give 1st (usually), followed by another (secondary) therapy
What is adjuvant therapy?
Combined with another modality; given after other therapy is used
What is salvage therapy?
For tumors that final to respond to initial chemotherapy
Have poor barrier function -> better to view them as signs of probably metastasis
Lymph nodes
Can be attempted for some tumors (colon into uterus, adrenal into liver, gastric into spleen); aggressive local invasiveness is different from metastatic disease
En bloc multiorgan resection
Tx: tumors of hollow visit causing obstruction or bleeding (colon Ca), breast CA with skin or chest wall involvement
Palliative surgery
No role in patients with clinically palpable nodes; you need to get after and sample these nodes
Sentinel lymph node biopsy
35% 5-year survival rate if successfully resected
Colon metastases to the liver
Prognostic indictors for survival after resection of hepatic colorectal metastases
Disease-free interval > 12 months, tumor number
Most successfully cured metastases with surgery
Colon CA in liver, sarcoma to the lung, but survival still low overall for these
One of the few tumors for which surgical debunking improves chemotherapy (not seen in other tumors)
Ovarian CA
Curable solid tumors with chemotherapy only
Hodgkin’s and non-Hodgkin’s lymphoma
T cell lymphomas
HTLV-1 (skin lesions) Mycosis fubgoides (Sezary cells)
HIV related malignancies
Kaposi’s sarcoma, non-Hodgkin’s lymphoma
Causes angiogenesis; involved in tumor metastasis
V-EGF (Vascular epidermal growth factor)
