principles of oncology pt 2 Flashcards
If this primary tx goal cannot be accomplished, the goal of cancer treatment shifts to:
1) palliation
2) treatment of symptoms
3) preservation of quality of life
difference between cure to cancer vs palliative care
cure = cancer treatments may be undertaken despite the certainty of severe and perhaps life-threatening toxicities
palliative = minimizing the toxicity of potentially toxic treatments becomes a significant goal
4 cancer tx types
- Surgery
- Radiation therapy (including photodynamic therapy)
- Chemotherapy
- Biologic therapy (including immunotherapy and gene therapy)
which type of cancer treatment is considered a local tx
- surgery
- radiation
which type of cancer tx is considered systemic tx
- Chemotherapy
- biologic therapy
which cancer tx is the most effective means of treating cancer
surgery
why is surgery used for cancer tx
- Cancer prevention (prophylactic mastectomy/colectomy)
- Diagnosis
- Staging
- Treatment (for both localized and metastatic disease)
- Palliation
?% of cancer patients cured by surgery
40%
However, 60% of solid tumors have metastasized and are not accessible for removal
what are the benefits of surgical tx for cancer even if it’s not fully curable with it
- Local control of tumor
- Preservation of organ function
- Debulking for subsequent treatments
- Palliative/Supportive care
- Placement of lines
- Control of effusions and ascites
- Removal of adhesions/strictures
- Reconstructive surgery
a physical agent that destroys cancer cells
radiation
The main goal of radiation therapy is to ?
deprive cancer cells of their cell division potential
how does radiation damage the cancer cells?
breaks in DNA that prevent replication and generates hydroxyl radicals from cell water
Cancer cells are not as efficient as normal cells in repairing the damage caused by radiation resulting in ?
differential cancer cell killing
Radiation therapy is most often administered locally, but systemic effects may develop depending on:
- volume of tissue irradiated
- dose fractionation,
- radiation fields
- individual susceptibility
The features that determine cell sensitivity to biologic effects of radiation is influenced by: (3)
- total absorbed dose
- number of fractions (delivering radiation in repeated doses to maximize exposure during cell division)
- time of treatment
Therapeutic radiation is delivered in 3 ways:
- teletherapy - focused beams of radiation generated at a distance and aimed at the tumor within the patient
- brachytherapy - encapsulated/sealed sources of radiation implanted directly into or adjacent to tumor tissues
- systemic therapy - radionuclides targeted in some fashion to a site of tumor……radioactive iodine for thyroid cancer
what is the most commonly used form of radiation therapy
Teletherapy with x-ray or gamma ray photons
what is the most commonly used form of radiation therapy
Teletherapy with x-ray or gamma ray photons
a component of curative therapy for several cancers:
Breast cancer, Hodgkin’s disease, head and neck cancer, prostate cancer, and gynecologic cancers.
Radiation therapy
what type of therapy can also be used for palliation such as relief of bone pain from metastatic disease, control of brain metastases
radiation therapy
what toxicities can happen from radiation therapy
-
Acute toxicities include mucositis, skin erythema (ulceration in severe cases), and bone marrow toxicity.
- Often these can be alleviated by interruption of treatment. -
Chronic toxicities are more serious
- Radiation carcinogenesis with secondary malignancy; pericarditis; myocardial infarction; thyroid failure; cataracts; lung fibrosis; arteritis; spinal cord transection
Though radiation therapy is most often administered to a local region, what other toxic effect can happen
systemic effects, including fatigue, anorexia, nausea, and vomiting, may develop
focused microwave radiation to induce thermal injury within a volume of tissue
Radiofrequency ablation
use of extreme cold to sterilize lesions in certain sites
Cryosurgery
Infusion of chemotherapeutic agents directly into the target area via vascular catheters
Chemoembolization
what agent may be used for the treatment of active, clinically apparent cancer
chemotherapy
can be administered in addition to surgery or radiation, after all clinically apparent disease has been removed
chemotherapy
Cancer drug treatments are of four broad types:
- Conventional cytotoxic chemotherapy agents - target DNA structure
- Targeted agents - molecular target important in either maintaining the malignant state or selectively expressed by the tumor cells.
- Hormonal therapies - work on the biochemical pathways underlying estrogen and androgen function
- Biologic therapies - induce a host immune response to kill tumor cells.
chemotherapy agents have what type of therapeutic index
narrow
Useful cancer drug treatment strategies have one of two valuable outcomes:
- induce cancer cell death
- tumor shrinkage with corresponding improvement in patient survival, or increase the time until the disease progresses. - induce cancer cell differentiation or dormancy
- loss of tumor cell replicative potential and reacquisition of phenotypic properties resembling normal cells.
Methotrexate
Antimetabolites - chemotherapy
5-fluorouracil (5-FU)
Antimetabolites - chemotherapy
MOA of Antimetabolites
Cause DNA damage indirectly
which antimetabolite prevents thymidine formation (required for DNA replication)
5-FU
which antimetabolite competes and counteracts folic acid, causing folic acid deficiency in cancer cell and cell death
Methotrexate
SE of antimetabolites
stomatitis, diarrhea, and myelosuppression
Vincristine, Vinblastine
Mitotic Spindle Inhibitors
Paclitaxel
Mitotic Spindle Inhibitors
SE of mitotic spindle inhibitors
alopecia, neuropathy, and myelosuppression.
which chemotherapy as a class are cell cycle phase–nonspecific agents
Alkylating Agents
what chemotherapy agents has MOA of covalently modify bases in DNA leading to cross-linkage of DNA strands or the appearance of breaks in DNA as a result of repair efforts
Alkylating Agents
Cyclophosphamide
Alkylating Agents
Chlorambucil
Alkylating Agents
Cisplatin
Alkylating Agents
which specific chemotherapy agent has SE of neuro-toxicity (stocking-glove), hearing loss, renal failure
Cisplatin
which chemotherapy agent:
- Produced by bacteria
- bind to DNA directly and can undergo electron transfer reactions to generate free radicals in close proximity to DNA
Doxorubicin (Anthracyclines)
which chemotherapy drug has a common SE of cardiotoxicity
Doxorubicin (Anthracyclines)
MOA of Topoisomerase inhibitor
inhibits DNA synthesis by forming a complex with topoisomerase II and DNA, causing breaks in DNA
Etoposide
Topoisomerase inhibitor
which drug has transient side effects but may lead to secondary leukemia with high doses
Topoisomerase inhibitor
signs of chemotherapy toxicity
- Bone marrow toxicity
- neutropenia
- anemia
- Thrombocytopenia - nausea
- mucositis
- diarrhea
- Skin Toxicity
- Alopecia
Tx for neutropenia
Colony stimulating factors (CSF)
Filgrastim
CSF
pegfilgrastim
CSF
sargramostim
CSF
SE of CSF
bleeding gums, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site.
Induction of peak levels of neutrophils is approximately ?
24 hrs
Tx for anemia from bone marrow toxicity
Transfusion; Epogen (erythropoiesis-stimulating agent)
tx for thrombocytopenia from bone marrow toxicity
Conservative monitoring
tx for nausea from chemotherapy toxicity
Ondansetron (anti-emetic)
Drugs most commonly associated with causing mucositis in the mouth and the gastrointestinal tract are:
cytarabine, 5-FU, and methotrexate.
Tx of mouth sores/mucositis
“Magic” Mouthwash
diphenhydramine, lidocaine, Maalox
Diarrhea can especially happen with what medication?
5FU infusions
careful attention to pt hydration and electrolyte levels
tx for diarrhea from chemotherapy toxicity
Loperamide (antimotility drug) (Imodium)
if there is no response from Loperamide, what is the alternative
Octerotide (somatostatin analogue)
opiate-based preparations
what can happen with skin toxicity from chemotherapy?
- Hyperpigmentation, alopecia, photosensitivity, nail changes, acral erythema, and generalized rashes.
- Acral erythema manifests as painful palms or soles accompanied by erythema, progressing to blistering desquamation and ulceration in its worst forms.
tx for skin toxicity
Supportive care; cold packs; sun protection
tx for alopecia
- Psychological support
- “chemo caps”
- reduce scalp temp - very controversial
what is the routine blood work for chemotherapy
- CBC
- CMP
- albumin
- AST/ALT
- Alk Phos
- Bilirubin
- BUN/Cr
- Ca++, Mg, K+, Na+
- Cl
- Glucose
- LDH
- Uric Acid - PT/aPTT
refers to the disorders that accompany benign or malignant tumors but are not directly related to mass effect or invasion
Paraneoplastic syndromes
Neoplastic cells can produce a variety of products that stimulate _______ responses
hormonal, hematologic, dermatologic, renal and neurologic responses
Clinical findings of Paraneoplastic Syndromes
may resemble disorders primarily:
Endocrine
Metabolic
Hematologic
Neuromuscular
Paraneoplastic Syndromes mechanism can be classified into three groups:
- effects initiated by a tumor product
- effects of destruction of normal tissues by tumor
- effects due to unknown mechanisms.
The paraneoplastic syndromes are clinically important for the following reasons:
(1) They sometimes accompany relatively limited neoplastic growth and may provide the clinician with an early clue to the presence of certain types of cancer.
(2) The metabolic or toxic effects of the syndrome may constitute a more urgent hazard to the patient’s life than the underlying cancer (eg, hypercalcemia, hyponatremia).
(3) Effective treatment of the tumor should be accompanied by resolution of the paraneoplastic syndrome and, conversely, recurrence of the cancer may be heralded by return of the systemic symptoms.
what are the Paraneoplastic Syndromes - Endocrine
- Hypercalcemia
- NSCLC, Breast, Renal cell, Adrenal, Prostate
- Usually due to parathyroid hormone related peptide - Hypoglycemia
- Hepatocellular carcinoma (impaired gluconeogenesis) - Gonadotropin secretion
- SCLC - Cushing’s syndrome
- SCLC, Adrenal, Thymoma
- ectopic production of ACTH by tumor - SIADH
- NSCLC, SCLC - ectopic production of vasopressin by tumor
what are the Paraneoplastic Syndromes - Hematologic
- Coagulopathy
- Breast, GI, Prostate - Erythrocytosis - due to ectopic production of erythropoietin
- Renal, Hepatocellular
what are the Paraneoplastic Syndromes - Neurologic
- Lambert-Eaton syndrome - immune mediated neurologic syndrome
- characterized by muscle weakness of the limbs
- SCLC - Subacute cerebellar syndrome - immune mediated cerebellar degeneration
- SCLC
- Characterized by dizziness, nausea, vertigo, tremor, and sometimes dysphagia and blurry vision
what are the Paraneoplastic Syndromes - Dermatologic
- Dermatomyositis
- SCLC, NSCLC
- inflammation of the muscles and skin, as well as joints, lungs, esophagus and heart - Acanthosis Nigricans - thickening of skin/brownish discoloration
- DM/obesity - fold of neck, under breast
- Cancer - mucous membranes
- GI adenocarcinomas
what is neutropenic fever
- above 38’C or a single temperature above 38.3’C in the presence of neutropenia
- absolute neutrophil count (ANC) less than 500 cells/mL (normal is above 1500)
symptoms of neutropenic fever
- vague and mild initially, but may rapidly progress to sepsis and death
- Symptoms also vary based on site of infection and source of infection
common viral causes of neutropenic fever
CMV, HSV, VZV
common bacterial causes of neutropenic fever
Staph, Strep. Enterococcus, H. flu, E. coli, Klebsiella, Pseudomonas
common fungal causes of neutropenic fever
Candida or Aspergillosis
what is an absolute CI for immunocompromised pt
rectal exams
Neutropenic Fever - Diagnosis and Tx (including meds)
- Cultures from all lumens, skin and line sites, blood, urine, sputum and stool
- Should be sent for bacterial, fungal and viral studies - Chest x-ray – may appear normal in patient with PNA, as it takes neutrophils to create an infiltrate
- Labs – CBC w/diff, CMP, coagulation panel and UA
- IV empiric antibiotic therapy should be initiated - AFTER CULTURE IS TAKEN
- Ceftazidime, Cefipime or Imipenem = antipseudomonal
- Aminoglycoside = g-
- Vancomycin = MRSA
if a pt is having more difficulty with lying down, weight bearing, sneezing, or coughing, what could be causing these symptoms
Spinal Cord Compression
what is the diagnostic study of choice for spinal cord compression
MRI
tx for spinal cord compression
High dose IV corticosteroids
Surgical decompression
Radiation
Hypercalcemia is caused by one of three mechanisms:
- Systemic effects of tumor-released proteins
- Direct osteolysis of bone by tumor
- Increased absorption of calcium due to increased active metabolite of Vitamin D
hypercalcemia is most commonly caused by
-
parathyroid hormone-related peptide secreted by the cancer cells
- activates the PTH receptor = osteoclastic activity and promoting renal reabsorption of calcium
- a marker of advanced cancer, with median survival ranging from 1 to 3 months
Most common cancers causing hypercalcemia are
myeloma, breast carcinoma, and non-small cell lung carcinoma (NSCLC)
SE of hypercalcemia
may include polydipsia, polyuria, generalized weakness, lethargy, anorexia, N/V, constipation, abdominal pain, AMS and psychosis
“stones, bones, groans, psychiatric overtones”
Hypercalcemia - Diagnosis and Tx
- Labs: Total serum calcium level and ionized calcium levels are elevated
- EKG: may show shortened QT, ST depression and AV blocks
- Treatment
- Hydration and forced diuresis
- Bisphosphonates - zoledronic acid, pamidronate IV
- Calcitonin - blocks bone resorption and also increases urinary calcium excretion by inhibiting renal calcium reabsorption, is second-line therapy
- Hemodialysis - definitive tx
A clinical syndrome that occurs 1 to 3 days following radiochemotherapy of most commonly hematologic malignancies
Tumor Lysis Syndrome
cause of tumor lysis syndrome
massive release of cellular material including nucleic acids, proteins, phosphorus, and potassium.
tumor lysis syndrome can MC cause what ?
Acute kidney injury
develop from the crystallization and deposition of uric acid and calcium phosphate within the renal tubules further exacerbating the hyperphosphatemia and hyperkalemia.
pt with tumor lysis syndrome also develop to combination of hyperkalemia and hypocalcemia that can lead to what other fatal SE
fatal cardiac arrhythmias
SE of tumor lysis syndrome
- lethargy
- N/V
- cloudy urine
- neuromuscular irritability
- muscular spasm
- seizure
- altered mentation associated with hypocalcemia
may show peaked T waves of hyperkalemia, as well as arrhythmias can be seen in what disease
tumor lysis syndrome
tx for tumor lysis syndrome
IV hydration and correction of electrolyte abnormalities
May require emergency hemodialysis
The development of an ____ may be the initial finding in a patient with cancer
effusion
Pleural and pericardial effusions most commonly caused by ?
lung and breast cancers
Malignant ascites associated with what type of cancers?
ovarian, colorectal, stomach, and pancreatic cancers.
s/s of Pericardial Effusion / Cardiac Tamponade
Patient may present with fatigue, chest heaviness, dyspnea, palpitations, cough and syncope
PE findings of pericardia effusion/cardiac tamponade
Tachycardia, narrowed pulse pressure, hypotension, distended neck veins, muffled heart sounds, and pulsus paradoxus
EKG of pericardia effusion/cardiac tamponade
sinus tachycardia, low QRS voltage and electrical alternans
what is the diagnostic tool of choice for Pericardial Effusion/Cardiac Tamponade
Transthoracic echocardiogram
what is the tx of choice for pericardial effusion/cardiac tamponade
echo-guided percutaneous pericardiocentesis under local anesthesia
The result of direct obstruction of the superior vena cava by malignancies such as compression of the vessel wall by right upper lobe tumors or thymoma and/or mediastinal lymphadenopathy
SVC Syndrome
The most common malignancy that causes SVCS is ?
bronchogenic carcinoma
Patients with SVC syndrome may present with a gradual onset of
- dyspnea, chest pain, cough and, facial and arm swelling
- cerebral edema is rare
PE findings of SVC syndrome
Distended neck, arm and chest veins, nonpitting edema of the neck, arm swelling, tongue and facial swelling and cyanosis
Chest x-ray may show a widened mediastinum is indicative of?
SVC syndrome
what is the diagnostic testing choice for SVC syndrome
Chest CT with contrast
what decreases the inflammatory response to tumor invasion and edema surrounding the tumor.
Glucocorticoids
what other tx instead of steroids could help with SVC syndrome depending on the tumor type
Intravascular stenting, chemotherapy and radiation
how can malignancy cause thromboembolic events
- Malignancy causes a hypercoagulable state
- Neoplastic cells and chemotherapy can cause intimal injury
- Obstructive tumors cause venous stasis
presentation of thromboembolic event
hx of dyspnea, fever, cough, DOE, pleuritic chest pain, leg pain or swelling, and rarely hemoptysis
PE findings of thromboembolic event
low-grade fever, tachypnea, tachycardia, pleural rub and unilateral lower extremity swelling
what is the diagnostic test of choice for a thromboembolic event
Ventilation-perfusion scan and spiral chest CT with contrast
tx for thromboembolic event
- Anticoagulation should be initiated immediately (unless contraindicated)
- heparin full-dose bolus and infusion
- LMWH (enoxaparin)
- Xarelto (rivaroxaban) - Thrombolytic therapy may be necessary with hemodynamic compromise and severe RV failure on echo
