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Cancer

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A broad range of diseases of multiple causes that can arise in any cell of the body capable of evading regulatory controls of proliferation and differentiation.

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Two major dysfunctions in cancer cells:

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- Defective proliferation - Defective differentiation

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Defective Proliferation

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Cancer cells proliferate at the same cells of the tissue it emerged from. However, they sometimes will produce more than 2 cells at mitosis. This causes an overall increase in cells that increases twofold everytime mitosis occurs, which can be a very rapid process depending on the tissue the cancer emerged from.

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Defective Differentiation

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Differentiation is when cells go from an immature state to a mature state with a specific responsibility. Cancer cells are poorly differentiated. In some instances, cancer can make differentiated cells dedifferentiate.

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Protooncogenes

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Promote growth and keeps the cell in its mature functioning state. - When it is mutated, it is exposed to carcinogens. Mutations can make this gene function as an oncogene (tumor-inducing gene). Oncogenes can change normal cells to malignant ones.

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Oncogenes

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Mutated protooncogenes. Change normal cells to malignant cells.

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Tumor Suppressor Genes

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Regulates cell growth by suppressing growth. - Mutations make them inactive, and so they no longer can suppress tumor growth.

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3 Stages of Cancer

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1) Initiation 2) Promotion 3) Progression

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Initiation

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Mutation in the cell's DNA genetic structure following exposure to a carcinogens (chemical, radiation, or viral agent). - 5% of mutations are inherited - Chemicals can be dangerous when exposed to them over long period of time - Radiation damages DNA in any tissue exposed to it - Viral carcinogens are oncogenes, as they infect and induce malignant transformation in cells (ex: HPV)

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Carcinogens

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Cancer-causing agents capable of producing cell alterations. Can be from chemical, radiation, or viral sources.

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Promotion

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*Reversible* proliferation of damaged cells is occurring in this stage because of promoting agents (smoking, high dietary fat, alcohol consumption, etc.). - Latent period is time span of 1-40 years between DNA damage and clinical evidence of cancer. Includes both initiation and promotion stage

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Tumor has to be...

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1 cm (1 billion cancer cells) before it is palpable. 0.5 cm tumor can be detected on MRI

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Remember:

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Things that occur in promotion stage are REVERSIBLE, whereas things that occur in the initiation stage are IRREVERSIBLE. *I*nitiation = *I*rreversible

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Progression

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Final stage of cancer that is characterized by increased growth rate of tumor, increased invasiveness, and metastasis

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Metastasis

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Multistep process in which tumor cells travel to distant sites via lymphatic system and vasculature.

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Most frequent sites of metastasis are:

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- Lungs - Bone - Brain - CSF - Liver - Adrenal Glands

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Hematogenous Metastasis

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1) Tumor cells penetrate blood vessels and enter circulation 2) Adhere to and penetrate small blood vessels of distant organs. Most tumor cells don't survive the process and are destroyed by immune system. However, some formation of a combination of tumor cells, platelets, and fibrin deposits may protect the tumor cells from destruction by immune system.

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Skip Metastasis

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Tumor cell gets trapped in the first lymph node it encounters or it skips the regional lymph nodes and goes to more distant ones first.

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Because cancer cells arise from normal cells...

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even though they are mutated, the immune response usually isn't adequate in killing them

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Tumor-Associated Antigens (TAAs)

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Antigens that cancer cells have on their surfaces.

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Immunologic Surveillance

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The immune systems response to TAAs

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Immunologic Escape

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Process by which cancer cells evade the immune system 1) Suppression of factors that stimulate T cells 2) Weak surface antigens 3) Development of tolerance to immune system 4) Suppression of immune system by products secreted by cancer cells 5) Induction of suppressor T cells by tumor 6) Blocking antibodies that bind TAAs, thus preventing recognition by T cells

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Oncofetal Antigens

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Type of tumor antigen that are found on both the surfaces and the inside of cancer and fetal cells. Means the cell has shifted to an immature metabolic pathway. Can be used as tumor markers in order to indicate tumor recurrence. Not 100% reliable.

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Benign Neoplasms

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- Well differentiated - No metastasis - Rarely recurs - Slight vascularity - Expansive growth - Cells are normal, similar to parent cells

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Malignant Neoplasms

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- Poorly differentiated - Capable of metastasis - Recurrence is possible - Moderate to extensive vasculature - Infiltrative and expansive growth - Cells are abnormal

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Classification systems provide a standardized way to:

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1) Communicate the status of the cancer to all members of the health care team 2) Assist in determining the most effective treatment plan 3) Evaluate the treatment plan 4) Predict prognosis 5) Compare like groups for statistical purposes

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Anatomic Classification

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Identified by the tissue of origin, the anatomic site, and the behavior of the tumor *Epithelial Tissue Tumors* Benign: -oma Malignant: -carcinoma *Connective Tissue Tumors* Benign: -oma Malignant: -sarcoma *Nervous Tissue Tumors* Benign: -oma Malignant: -oma *Hematopoietic Tissue Tumors* Malignant: -oma and -emia

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Histologic Grading

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Appearance of cells and the degree of differentiation are evaluated pathologically. 4 grades (Grades I-IV, and X) are used to evaluate abnormal cells based on the degree to which the cells resemble the tissue of origin.

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Dysplasia

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Cells that look abnormal under a microscope

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Grade I

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Cells differ slightly from normal cells (mild dysplasia) and well differentiated

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Grade II

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Cells are more abnormal (moderate dysplasia) and moderately differentiated

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Grade III

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Cells are very abnormal (severe dysplasia) and poorly differentiated

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Grade IV

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Cells are immature and primitive (anaplasia) and undifferentiated; cell of origin is difficult to determine

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Grade X

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Grade cannot be assessed

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Clinical Staging

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Determines anatomic extent of the malignant disease process by stages (0-IV).

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Stage 0

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Cancer in situ (refers to neoplasm whose cells are localized and show no tendency to invade or metastasize to other tissues)

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Stage I

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Tumor limited to the tissue or origin; localized tumor growth

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Stage II

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Limited local spread

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Stage III

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Extensive local and regional spread

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Stage IV

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Metastasis

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TNM Classification System

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Determine anatomic extent of disease involvement according to three parameters: *T* tumor and invasiveness *N* presence or absence of regional spread to lymph nodes *M* metastasis to distant organ sites 0: No evidence of primary tumor is: Carcinoma in situ 1-4: ascending degrees of TNM involvement x: TNM cannot be determined/measured/found

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Surgical Staging

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Extent of disease as determined by surgical excision, exploration, and/or lymph node sampling

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Seven Warning Signs of Cancer (CAUTION)

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*C*hange in bowel or bladder habits *A* sore that does not heal *U*nusual bleeding or discharge from any body orifice *T*hickening or a lump in breast or elsewhere *I*ndigestion or difficulty swallowing *O*bvious changes in a wart or mole *N*agging cough or hoarseness

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Goals of public education are to:

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1) Motivate people to recognize and modify behaviors that may negatively impact health 2) Encourage awareness of and participation in health-promoting behaviors

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A diagnostic plan for the person in whom cancer is suspected includes...

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- Health Hx - Identification of risk factors - Physical exam - Any specific Dx studies - Biopsy (only definitive way to Dx cancer)

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Goal of cancer treatment is:

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- *Cure*: treatment is offered that is expected to have the greatest chance of disease eradication. May involve chemo/surgery alone or in conjunction w/chemo, biologic, or targeted therapies - *Control*: Cancer cannot be completely eradicated but are responsive to anticancer therapies and can be maintained for long periods with therapy. - *Palliative*: Relief or control of symptoms and the maintenance of a satisfactory quality of life are the primary goals rather than cure or control of the disease process.

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Surgical Therapy

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- *Prevention*: Can be used to eliminate or reduce risk of cancer development. Prophylactic removal of nonvital organs have been successful in reducing incidence of some malignancies - *Cure/Control*: Remove all or as much of tumor as possible while sparing normal tissue. Debulking is done when tumor cannot be completely removed. Can make chemo/radiation more effective. - *Palliative*: Following surgical procedures can maximize bodily function or facilitate cancer treatment: feeding tube insertion, CVA device to deliver chemo agents, prophylactic surgical fixation of bones

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Chemotherapy

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Goal is to eliminate or reduce the number of malignant cells present in the primary tumor and metastatic tumor site(s). Most common administration sites are CVA devices, peripheral central venous catheter, or implanted infusion ports (All IV methods). These sites reduce risk of extravasation as chemo drugs are very toxic to skin and cause necrosis. Nurse needs to be aware of any redness, swelling, pain at site if infusing via IV.

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Cisplatin (Platinol)

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Alkylating Agent. Cell cycle phase - nonspecific agents. Bind to DNA, inhibiting replication, which kills cells. - Ototoxicity can occur - Peripheral neuropathy can occur (sensory loss, numbness and tingling, and difficulty walking) - Contraindicated in Pt allergic to mannitol or platinum-containing formulas - No PO form

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Doxorubicin (Adriamycin)

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Anti-tumor Antibiotic. Cell cycle phase- nonspecific agents. Binds to DNA and inhibits synthesis of DNA and transcription of RNA - Urine may appear red, red/orange, orange, pink 1-2 days after dose - Nail beds darken - Can interfere w/pumping action of heart so there is a "lifetime max dose" that Pt can receive - Pt w/CHF cannot receive this drug - Baseline heart eval is recommended before starting drug

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Cyclophosphamide (Cytoxan)

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Alkylating Agent. Cell cycle phase - nonspecific agents. Bind to DNA, inhibiting replication, which kills cells. - Give w/food or after meals - Do not crush/chew tabs - Void frequently in first 24 h after receiving drug

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5-Fluorouracil (Fludara)

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Antimetabolites. Cell cycle phase - specific agents. Interferes w/pyrimidine (building block needed for DNA synthesis) metabolism. - Severe central neurotoxicity can occur (weakness, agitation, confusion, seizures, and/or coma) - Hemolytic anemia can occur - Tumor lysis syndrome can occur

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Vincristine sulfate (Oncovin)

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Mitotic Inhibitors. Cell cycle phase - specific agents. Inhibits mitosis. - No PO form - Peripheral neuropathy can occur (sensory loss, numbness and tingling, and difficulty walking) - Reflexes need to be checked frequently in order to see if dose needs to be changed

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Intraarterial Chemotherapy

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Delivers drug to tumor via arteries supplying tumor

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Intraperitoneal Chemotherapy

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Delivers drug to peritoneal cavity for treatment of peritoneal metastasis - Short-term therapy calls for Silastic catheters placed percutaneously or surgically - Implanted port is used for longer-term therapy - Drug is infused into peritoneum in 1-2 L fluid and dwells there for 1-4 hrs, after which peritoneum is drained

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Intrathecal or Intraventricular Chemotherapy

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Used to treat metastasis to the CNS - One method involves lumbar puncture and injection of drug into subarachnoid space, but this results in uneven drug distribution - Using an Ommaya reservoir results in more uniform drug distribution. Makes Pt not have to have multiple lumbar punctures

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Intravesical Bladder Chemotherapy

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Instillation of drug into bladder for 1-3 hours and then drained

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Chemo side effects are the result of...

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destruction of normal cells

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Acute Toxicity

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Occurs during and immediately after drug administration - Anaphylactic/hypersensitivity reaction - Extravasation/flare reaction - Anticipatory N/V - Cardiac dysrhythmias

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Delayed Effects

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- Delayed N/V - Mucositis - Alopecia - Skin rashes - Bone marrow suppression - Altered bowel function (D/C) - Variety of cumulative neurotoxicities

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Chronic Toxicities

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- Damage to organs such as heart, liver, kidneys, and lungs - Can be long-term effects that occur during/immediately after treatment and persist, or late effects that are absent during treatment and manifest later

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Chemotherapy is most effective when...

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- Tumor burden is low - Therapy is not interrupted - Pt receives intended dose

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Radiation

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Emission and distribution of energy through space or a material medium. Breaks the chemical bonds of DNA. The DNA is damaged, and the cell dies.

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Radiation Therapy

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Treats a carefully defined area of the body either by itself or in combination with surgery or chemotherapy. It can also be used as palliative treatment for symptom control in patients with metastatic disease. It is not appropriate as the primary treatment for a systemic disease.

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Simulation

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A part of radiation treatment planning used to determine the optimal treatment method by focusing on accurately localizing the tumor/target field and ensuring set-up position reproducibility

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Teletherapy (External Beam Radiation, EBRT)

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- Most common radiation therapy - Delivers ionizing radiation to kill cancer cells - Pt is exposed to radiation from a linear accelerator

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Brachytherapy (Internal Radiation Therapy)

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- Consists of implantation or insertion of radioactive materials directly into the tumor (interstitial) or in close proximity to the tumor (intracavitary/intraluminal) - Allows for direct delivery of radiation to target w/minimal exposure to surrounding healthy tissue - Implants can be permanently placed (radioactive seeds). These Pt are not considered radioactive. Isotopes decay over time and are no longer radioactive - Temporary seeds may be delivered through catheters to the target site for specified amounts of time and then withdrawn. Pt is radioactive during therapy but not after removal of seeds. Can be given in low-dose-rate (LDR) or high-dose-rate (HDR) - Organize care to limit time in presence of Pt, and make sure Pt knows why you are limiting time w/them. - Use shielding and wear film badge

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Myelosupression (Bone Marrow Suppression)

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Most common effect of chemo (can also occur w/radiation) - Can result in infection, hemorrhage, extreme fatigue - Radiation to regions of the body that contain the most bone marrow (pelvis, thoracic/lumbar vertebrae) result in most severe myelosuppression - Nurse needs to monitor CBC (especially neutrophil, platelet, RBC). Know that it will reach nadir 7-10 days after initiation of treatment - Neutropenia (low WBC) is serious risk factor for infection and sepsis. Severe neutropenia will cause delay of treatment or modification of treatment. Hand hygiene is of utmost importance. Monitor temperature as any sign of infection needs to be treated promptly. Neulasta is used to reduce chemo-induced neutropenia, also used prophylactically - Anemia has a late onset (3-4 months after initiation of treatment). Erythropoietin can be given. Blood transfusion is indicated in extreme cases. - Fatigue is caused by anemia, accumulation of toxic substances in body, the need for extra energy to repair and heal damaged cells, and lack of sleep caused by drugs

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GI Effects

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- Intestinal mucosa is one of the most sensitive tissues to treatments. Causes N/V/D and mucositis - Give zofran prophylactically

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Nadir

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The lowest CBC

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Pegfilgrastim (Neulasta)

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Stimulates WBC production - Can cause bone pain, N/V

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Erythropoietin

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Stimulate RBC production - Can cause HTN, thrombosis, headaches

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Table 16-11, Pgs 266 & 267

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Nursing Management of Problems Caused by Chemo and Radiation Therapy

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Biologic and Targeted Therapy

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- Can be used alone or in combination w/surgery, radiation, and/or chemo - *Biologic therapy* consists of agents that modify the relationship between the host and the tumor by altering the biologic response of the host to the tumor cells - *Targeted Therapy* interferes with cancer growth by targeting specific cell receptors and pathways that are important in tumor growth

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Interferon (Roferon-A, Intron A)

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- Inhibits DNA and protein synthesis, suppresses cell proliferation, increases cytotoxic effects of NK cells - No PO form - Do not take w/aspirin - Causes dark urine - Myelosuppression - Capillary Leak Syndrome and pulmonary edema can occur

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Interleukin-2 (Aldesleukin [Proleukin])

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- Stimulates proliferation of T and B cells and activates NK cells - Capillary Leak Syndrome and pulmonary edema can occur - Myelosuppression

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Hematopoietic Growth Factors

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Used to support cancer Pt through treatment.

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Hematopoietic Stem Cell Transplantation (HSCT)

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An effective, life-saving procedure for a number of malignant and nonmalignant diseases. The goal is cure. The approach is to eradicate diseased tumor cells and/or clear the marrow of its components to make way for engraftment of the transplanted, healthy stem cells.

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Allogeneic Transplantation

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Stem cells are acquired from a donor who has been determined to be human leukocyte antigen (HLA)-matched to the recipient.

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Syngeneic Transplantation

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A type of allogeneic transplant that involves obtaining stem cells from one identical twin and infusing them into the other.

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Autologous Transplantation

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Pt receives own stem cells back following myeloablative (destroying bone marrow) chemotherapy.

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Plerixafor (Mozobil)

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SQ drug that is given in combination G-CSF (like neulasta) that boosts number of stem cells released from bone marrow into the bloodstream

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Conditioning Regimen

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- Pt receive myeloablative dosage of chemo w/w/o adjunctive radiation to treat underlying disease in conditioning - Body needs to be prepared for autologous transplantation to ensure collection of optimally functioning stem cells in adequate numbers. Conditioning is done after stem cells have been harvested.

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Complications of HSCT

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Infections and graft vs. host disease. Prophylactic antibiotics reduce incidence of infection.

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Complications Resulting From Cancer: Nutritional Problems

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- Protein and calorie malnutrition characterized by fat and muscle depletion - Avoid extremes of temp, tobacco, alcohol, spicy/rough foods, other irritants - Encourage nutritional supplements (Ensure) - Weigh Pt 2x week - Referral is needed once Pt looses 5% weight - Once 10 lb (4.5 kg) weight loss occurs, it's difficult to maintain nutritional status - Taste may be altered (dysgeusia). Teach Pt to avoid disliked food and to experiment w/spices.

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Complications Resulting From Cancer: Infection

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- Primary cause of death in Pt w/cancer - Usual sites of infection are lungs, GU system, mouth, rectum, peritoneal cavity, and blood. Results from ulceration and necrosis. - Tell Pt to call HCP if temp is 100.4 or greater - Assess for S/S fever - B/c Pt are often neutropenic when infection develops, infection can cause significant morbidity

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Complications Resulting From Cancer: Oncologic Emergencies (focus on)

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- *Superior Vena Cava Syndrome (SVCS)*: Results from obstruction of superior vena cava by tumor or thrombosis. S/S: facial edema, periorbital edema, head/neck/chest vein distention, headaches, seizures. Management includes radiation therapy to site of obstruction but chemo may be administered for tumors that are sensitive to it. - *Spinal Cord Compression (SCC)*: Neurologic emergency caused by tumor in epidural spaces of the spinal cord. S/S: back pain that is intense, localized, and persistent, vertebral tenderness, aggravated by Valsalva maneuver, motor weakness/dysfunction, sensory paresthesia and loss, autonomic dysfunction. Managed by radiation therapy along w/corticosteroids - *Tumor Lysis Syndrome (TLS)*: Complication in which rapid release of intracellular components in response to chemo. When the tumor is destroyed, the components are released into the bloodstream. S/S: 4 hallmark signs: Hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia. Occurs within first 24-48 hr after initiation of chemo. Can persist for 5-7 days. Goal of management prevents renal failure and severe electrolyte imbalances. Primary treatment includes increasing urine production using hydration therapy and decreasing uric acid concentrations w/allopurinol.

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Complications Resulting From Cancer: Oncologic Emergencies continued (don't focus on these)

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- *Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)*: Abnormal or sustained production of ADH by tumor cells w/resultant water retention and hypernatremia. S/S: weight gain w/o edema, anorexia, N/V, personality changes, seizures, oliguria, decreased reflexes, coma. Treated by correcting sodium-water imbalance. Lasix is helpful with this. Monitor sodium level as correcting SIADH can result in seizures or death. - *Hypercalcemia*: Occurs in metastatic disease of the bone or when PTH-like substance is secreted by cancer cells. S/S: apathy, depression, fatigue, muscle weakness, ECF changes, polyuria, nocturia, anorexia, N/V. Treated with Bisphosphonates (Zometa, Aredia) as they inhibit action of osteoclasts and reduce serum calcium levels. - *Third Space Syndrome*: Shifting of fluid from vascular space to interstitial space. Occurs secondary to surgical procedures, biologic therapy, or septic shock. S/S: Hypovalemia, hypotension, tachycardia, low central venous pressure, decreased urine output. Treated w/fluid, electrolytes, plasma protein replacements. Hypervalemia can occur during recovery and so reduction in fluid administration and fluid balance monitoring occurs. - *Cardiac Tamponade*: Results from fluid accumulation in pericardial sac, constriction of pericardium by tumor, or pericarditis secondary to radiation therapy to chest. S/S: heavy feeling over chest, dyspnea, tachycardia, cough, dysphagia, hiccups, N/V, diaphoresis. Emergency management is aimed at reducing fluid around the heart, surgically

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Manage cancer pain...

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ATC w/coverage for breakthrough pain. Pain assessments need to be done often and comprehensively.

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Your nursing care can facilitate the development of a...

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hopeful attitude about cancer and support the patient and the family during the various stages of the process of cancer (See Table 16-19, Pg. 280).

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Cancer Survivorship

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- Cancer survivors experience a variety of long-term and late sequelae following treatment, including a greater risk of functional impairment, noncancer-related death and comorbidities, including heart disease, diabetes, osteoporosis, and others. - The impact of a cancer diagnosis can affect many aspects of life, with survivors commonly reporting financial, vocational, marital, and emotional concerns long after treatment is over. - The psychosocial effects can play a profound role in a patient's life after cancer, with issues related to living in uncertainty being frequently encountered.

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Culturally Competent Care r/t Cancer

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- Underserved populations are at risk for late-stage disease at time of diagnosis. - Nurses need to know how to assess for cultural differences, identify barriers to care, and adapt care to meet specific cultural needs.

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