ONCOLOGY BASICS

Cancer: A Genetic Disease

Mutations​ in genes that control cell growth and divison are responsible for cancer.
(cell proliferation and differentiaion)
Carcinogens DNA mutations

Cancer and Genes

- ​Oncogenes​ are genes that, when mutated, actively promote cell proliferation
- ​Tumor suppressor genes​ are genes that, when mutated, fail to repress cell division

Oncogenes
...the ​overexpression​ of certain genes
...the ​abnormal activity​ of certain genes
...their ​mutant​ protein products

Tumor Suppressor Genes

Many ​cancers​ involve the inactivation of genes whose products play important roles in
regulating the cell cycle

Knudson’s Two-Hit Hypothesis

- when tumor suppressor genes are mutated, a predisposition to develop cancer often
follows a dominant pattern of inheritance
- the mutation is usually a loss-of-function mutation in the tumor suppressor gene
- cancer develops only if a second mutation in somatic cells knocks out the function of the
wild-type allele

Cancer Genetics
- a series of somatic alterations in DNA that result in ​unrestrained cellular proliferation
- most involve actual sequence changes in DNA (ie mutations)

- result as a consequence of:

> random replication errors
> exposure to carcinogens (eg radiation)
>faulty DNA repair processes
- mostly arise sporadically
-familial clustering of cancers occurs in certain families that carry a germline mutation in cancer
gene

Named for site of origin

Carcinoma - epithelial cells; cover external and internal body surfaces (90%)
Sarcoma - supporting tissue; bone, cartilage, fat, connective tissue, pancreas, liver
Lymphoma & Leukemias - bld & lymphatic tissue (leukemia reserved for cancers that
reside in bldstream not as solid tissue)

Comparison of Normal and Tumor Growth in the Epithelium of the Skin

Phenotypic Characteristics of Malignant Cells

- deregulated cell proliferation - failure to differentiate
- loss of normal apoptosis pathway - genetic instability
- loss of replicative senescence - inc angiogenesis
- invasion - metastasis
- evasion of the immune system - shift in cell metabolism
- nonresponsive to external growth-inhibiting signals

Stages in the Process of Invasion and Metastasis

Cell Cycle Checkpoints
● Transitions between different phases of the cell cycle (G1, S, G2, and M) are regulated
at checkpoints
● A ​checkpoint ​is a mechanism that halts the progression through the cycle until a critical
process is completed.

Cyclins and CDK’s

● Important checkpoint proteins are the ​cyclins​ and the ​cyclin dependent kinases (CDK’s);
complexes formed between cyclins and CDK’s cause the cell cycle to advance.
● The CDK’s ​phosphorylate ​target proteins but are inactive unless they are assoc with a
cyclin protein
● Cell cycling requires the alternate ​formation and degradation ​of cyclin/CDK complexes

Establishing Cancer Diagnosis

● Biopsy- Histopathologic Diagnosis
○ Fine Needle aspiration biopsy
○ Core-needle biopsy
○ Incisional Biopsy
○ Excisional Biopsy
● “Liquid Biopsy”
○ Analyzes different kinds of tumor materials, such as DNA, RNA, proteins
○ Detects molecules in various bodily fluids, eg. blood, CSF, urine, etc
Cancer Staging
● TNM Staging
○ Tumor
○ Node
○ Metastasis
● Importance:
○ Prognostication
○ Treatment Plan
Cancer Treatment
Local treatment
1. Surgery
2. Radiation Therapy
● External beam RT
● Brachytherapy
Systemic treatment
1. Chemotherapy
● Neoadjuvant
● Adjuvant
● Palliative
2. Hormonal therapy
3. Biological therapy
4. Immunotherapy

Oncologic emergencies
● Pressure or obstruction caused by a space occupying lesion.
● Metabolic or hormonal problem (​paraneoplastic syndromes)
● Treatment related complications

Structural-obstructive oncologic emergencies

● SVC syndrome
● Spinal cord compression
● Pericardial effusion or tamponade
 ● Intestinal obstruction
● Urinary obstruction
● Malignant biliary obstruction
● Increased ICP
● neoplastic meningitis
● Seizures
● Pulmonary and intracerebral leukostasis
● Airway obstruction

Metabolic emergencies

● Hypercalcemia
● SIADH
● Lactic acidosis
● Adrenal insufficiency

Treatment related emergencies

● Tumor lysis syndrome

● Human antibody infusion reactions
● HUS
● Neutropenia & Infection
● Pulmonary infiltrates
● Neutropenic enterocolitis
● Hemorrhagic cystitis
● Hypersensitivity reactions to antineoplastic drugs

Superior Vena Cava Syndrome

● SVC obstruction with severe reduction in venous return from head, neck and upper
extremities
● Etiologies:
○ Malignant tumors, e.g. lung cancer, lymphoma, metastatic tumors
○ Benign causes, e.g. central venous access catheters, pacemakers, defibrillator
leads
○ Other causes: benign tumors, aortic aneurysms, thyromegaly, thrombosis,
fibrosing mediastinitis
● Clinical manifestations:
○ Neck and facial swelling
○ Dyspnea
○ Cough
○ Hoarseness
○ Hemoptysis
○ Dysphagia
 ○ Pain
○ Dizziness
○ Syncope
○ Lethargy
● Chest X-ray
○ Widening of the superior mediastinum, most commonly on the right side

Diagnosis of SVC
Syndrome
● CT Scan:
 ○ Diminished or absent opacification of central venous structures with prominent
collateral venous circulation

Treatment of SVC Syndrome

● May give temporary
symptomatic
relief of pain
○ Diuretics with low salt diet
○ Head elevation
○ Oxygen therapy
● Glucocorticoids - for lymphoma
● Radiation therapy - for NSCLC and other metastatic solid tumors
● Chemotherapy - for small-cell lung CA, lymphoma, germ cell tumor
● Use of intravascular self-stenting stents - for palliation of SVCS recurrence

Pericardial Effusion/Tamponade
● Malignant pericardial diseases seen in :
○ Lung cancer
○ Breast cancer
○ Leukemia
○ Lymphomas
● Symptomatic pericardial disease:
○ Irradiation
○ Drug-induced pericarditis
○ Hypothyroidism
○ Idiopathic pericarditis
 ○ Infection
○ Autoimmune diseases
● Common symptoms:
○ Dyspnea
○ Cough
○ Chest pain
○ Orthopnea
○ Weakness
● Frequent PE findings:
○ Pleural effusion
○ Sinus tachycardia
○ Jugular venous distention
○ Hepatomegaly
○ Peripheral edema
○ Cyanosis
● Treatment
○ Pericardiocentesis with or without the introduction of sclerosing agents (eg
bleomycin, mitomycin C or tetracycline)
○ The creation of a pericardial window, complete pericardial stripping
○ Cardiac irradiation
○ Systemic chemotherapy
● Pericardiocentesis
Malignant Spinal Cord Compression
● Compression of the spinal cord and/ot cauda equina by an extradural tumor mass
● Minimum radiologic evidence for cord compression--indentation of the theca at the level
of clinical features
● Occurs in 5-10% of patients with cancer
● Epidural tumor - first manifestation of malignancy in about 10% of patients
● Lung cancer - the common cause
● Thoracic spine - the most common site (70%), followed by the lumbosacral spine (20%)
and the cervical spine (10%)
● Involvement of multiple sites seen jn breast and prostate carcinoma
● Develops when metastases to vertebral body or pedicle enlarge and compress the
underlying dura
● Most common initial symptom
○ Localized back pain and tenderness due to involvement of vertebrae by tumor
● Lhermitte’s sign
○ A tingling or electric sensation down the back and upper and lower limbs upon
flexing or extending the neck
○ An early sign of cord compression
● Loss of bowel or bladder control
● Ataxia of gait without motor and sensory involvement
● PE finding:
 ○ Pain induced by straight leg raising, neck flexion or vertebral percussion
○ Numbness and paresthesias in the extremities or trunk
○ Loss of sensibility to pinprick, vibration or position
○ Weakness, spasticity and abnormal muscle stretching
○ (+) extensor plantar reflexes reflects significant compression
○ Brisk deep tendon reflexes. Motor and sensory loss usually precedes sphincter
disturbance
○ Autonomic dysfunction
● Cauda equina syndrome ​is characterized by :
○ Low back pain
○ Diminished sensation over the buttocks, posterior-superior thighs, and perineal
area in saddle distribution
○ Rectal and bladder dysfunction
○ Sexual impotence
○ Absent bulbocavernous , patellar and Achilles reflexes
○ Variable amount of lower extremity weakness
- Reflects compression of nerve roots as they form the cauda equina after leaving the
spinal cord.
- Majority are primary tumors of glial or nerve sheath origin; metastases are very rare.
Treatment for Spinal Cord Compression
● Radiation therapy plus glucocorticoids is generally the initial treatment of choice
● Indications for surgical intervention:
○ Unknown etiology
○ Failure or radiation therapy
○ A radioresistant tumor type (e.g., melanoma or renal cell cancer)
○ Pathologic fracture dislocation
○ Rapidly evolving neurologic symptoms
Pulmonary and Intracerebral Leukostasis
● Hyperleukocytosis and the leukostasis syndrome
- a potentially fatal complication of acute leukemia (particularly myeloid leukemia)
that can occur when the peripheral blast cell count is >100, 000/mL.

● Frequency of hyperleukocytosis:
○ 5-13% in acute myeloid leukemia (AML)
○ 10-30% in acute lymhoid leukemia
○ Rare in lymphoid leukemia.
Pulmonary and Intracerebral Leukostasis
Clinical Manifestations:
• Stupor, headache, dizziness, tinnitus, visual disturbances, ataxia, confusion, coma, or sudden
death
• Papilledema, retinal vein distention, retinal hemorrhages, and focal deficit may be present
Treatment:
• IV hydration
• Administration of 600cGy of whole-brain irradiation can protect against this complication
• Rapid institution of antileukemic therapy
• Hydroxyurea 3-5 grams

Humoral Hypercalcemia of Malignancy (HHM)

• Occurs in 20% of cancer patients
• Most common in cancers of the lung, head and neck, skin, esophagus, breast, and
genitourinary tract and in multiple myeloma and lymphomas
• Cause: overproduction of PTHrP
• Clinical Manifestations:
-Fatigues, mental status changes, dehydration of symptoms of nephrolithiasis
• Treatment:
-Saline rehydration (typically 200-500 mL/h)-Forced diuresis with furosemide (20-80 mg IV)
-Bisphosphonates such as pamidronate (60-90 mg IV), zoledronate (4-6 mg IV), and etidronate
(7.5 mg/kg per day PO for 3-7 consecutive days)
-Dialysis in severe hypercalcemia
-Calcitonin (2-8 U/kg SC every 6-12 hours)
-Glucocorticoid treatment (e.g., 40-100 mg PO in four divided doses)
Tumor Lysis Syndrome
• Caused by the destruction of a large number of rapidly proliferating neoplastic cells
• Characterized by:
-Hyperurecemia
-Hyperkalemia
-Hyperphosphatemia
-Hypocalcemia
-Acidosis
• Acute renal failure occurs frequently

Tumor Lysis Syndrome

Associated with:
● Treatment of Burkitt’s Lymphoma, acute lymphoblastic leukemia, and other rapidly
proliferating lymphomas
● Chronic leukemias and, rarely, with solid tumors
● Chronic lymphocytic leukemia, after treatment with nucleosides like fludarabine
● Administration of glucocorticoids, hormonal agents such as letrozole and tamoxifen, and
monoclonal antibodies such as rituximab and gemtuzumab
TLS usually occurs during or shortly (1-5 days) after chemotherapy

Recognition of risk and prevention

● Allopurinol
● Urinary alkalinization
● Aggressive hydration
Use of rasburicase in cases of elevated uric acid levels refractory to standard preventive
approach
● Contraindicated among patients with glucose-6-phosphate dehydrogenase deficiency
Hemodialysis
Read on the following
● Infections in patient with cancer
● Breast cancer
● Lung cancer
● Prostate cancer
● GI cancer
● Cancer of unknown primary