End Stage Disease Progression and Complications – Oncologic Disorders (Learning Hospice)

• Breast cancer is the most frequently diagnosed and is the leading cause of death from cancer in women worldwide.
• Lung cancer is the most frequently diagnosed and the leading cause of death from cancer in men worldwide.
• Cancer is the second most common cause of death in the United States following heart disease.

Cancer refers to a group of diseases that are characterized by uncontrolled growth and spread of abnormal of mutated cells that can be caused by external and internal factors. Mutated cells have certain characteristics as follows:

• can avoid apoptosis (cell death)
• resist normal aging process
• can replicate outside normal controlling mechanisms
• produce chemicals that dissolve surrounding tissue
• invade other parts of the body
• overcome the immune system

TNM staging system:

T: size and extent of the primary tumor

N: presence or absence of lymph node

M: presence or absence of distant metastasis

Stages 0-IV are assigned based on TNM criteria with stage 0 being in situ and IV being most advanced disease. Example: T4, N3, M1 Colon Cancer is considered Stage IV Cancer with Metastasis

Process of disease progression:

1. Invasion – process where cells continue to divide and with increased bulk, pressure, and secretion of enzymes, cancer is spread locally or into surrounding structures
2. Angiogenesis – generation of blood vessels by the tumor site, which allows easier access for the tumor cells to enter the bloodstream; this increases risk of metastatic spread
3. Metastasis – the spread of cancer cells from a primary tumor site to distant sites in the body through one of several routes
   • direct invasion into an organ
   • seeding within a body cavity
   • spread through the lymphatic system
   • dissemination via capillaries and veins (most metastases occur this route)

Something about Genetics:

• Hereditary cancer syndromes are attributed to genes that are passed from either parent to their children; 5-10% of cancers are hereditary; family history of maternal and paternal lineage is vital to determine those at risk and should include race/ethnicity, current health status, current age or age at death, types of primary cancer, age at diagnosis for each cancer, bilaterality of paired organs, environmental exposures; Hereditary syndromes that have evidence showing improved survival or benefit of early detection include hereditary breast and ovarian syndromes, hereditary colorectal syndrome, multiple endocrine neoplasias, Li-Fraumeni syndrome; Epigenetics leads to the reduced expression of the DNA repair genes and thereby contributes to genetic instability.

• Futures of Hereditary Cancers
  1. Early age of onset
  2. Autosomal dominant inheritance pattern
  3. Cancer in 2 or more close relatives
  4. Bilaterally in paired organs
  5. Multiple primary cancers in 1 person

• Ethical and social issues surrounding genetic testing
  1. Autonomy- the patient has the righ to choose genetic testing or refuse testing regardless of their risk assessment
  2. survivor guilt of family members who did not inherit a genetic mutation
  3. transmitter guilt of a family member who passed on the genetic mutation
  4. increased anxiety and anticipatory grief in individuals who have or are determined to be at high risk for developing a malignancy, including higher risk of suicide potential
  5. stigmatization of the family members who are found with a genetic mutation
  6. potential for unethical practices by clinical researchers
  7. payer source discrimination for testing; increased risk for “dropping” patients if malignant trend identified in family.

Treatment in Cancer:

• Surgery- used for prevention, diagnosis, staging, curative therapy or palliation
  • high potential for cure when disease is localized
  • serves as primary mechanism for obtaining necessary tissue for pathologic diagnosis of cancer
• Radiation- approximately 60% of patients with cancer will receive radiation at some point of their treatment.
  • Typical side effects- skin reaction, fatigue, weight loss, myelosuppression, alopecia, nausea and vomiting, mucositis, xerostomia
  • Side effects can be acute, subacute, and late
    • Acute- site specific, short-term effects such as mucositis, xerostomia (dry mouth), gastrointestinal distress, fatigue, or tissue ulceration; typically resolve at the conclusion of treatment
    • Subacute- effects that appear within weeks to a few months after completion of treatment such as pneumonitis, rib fractures, renal damage.
    • Late- dependent on dose, volume, and length of radiation and can occur after 6 months following treatment such as small or large bowel injury, infertility, following abdominal treatment.
• Chemotherapy- can be utilized for cure, control of disease, or palliation
  • Expected side effects: stomatitis (infomation of the mouth), alopecia, myelosuppression (neutropenia, anemia, thrombocytopenia), nausea with and without vomiting, anorexia, diarrhea, fatigue
  • Long-term side effects/toxicities: occur weeks to months after administration
    • Cardiotoxicity (similar in presentation to congestive heart failure with dyspnea, cough, pedal edema, poor response to diurectics or digitalis
    • Neurotoxicity
      1. Can occur in the periphery (extremities) or in the autonomic nervous system (e.g., constipation, ileus, impotence, urinary retention, postural hypotension)
      2. Most common effect – chemotherapy-associated peripheral neuropathy (CAPN). Starts with a stocking and glove (which feels like the patient is wearing socks and/or gloves) distribution with report of burning, tingling, numbness, or vibratory sensations
  • • Pulmonary toxicity- Presents as a drug-induced pneumonitis or restrictive lung disease with dyspnea, unproductive cough, basilar rales, tachypnea, and low grade fever
    • Hepatotoxicity- Presentation includes elevated hepatic enzymes and can progress to jaundice, hypatomegaly, encephalopathy, and abdominal pain. Can lead to cirrhosis in a few patients
    • Nephrotoxicity- Kidney damage can range from direct renal cell damage to obstructive nephropathy

End-stage disease oncologic disorders may vary depending on the type of cancer and the areas of metastasis but often includes the following:

1. Pain: This is the most common complication due to pressure from tumors on surrounding tissue, causing ischemia and nerve compression. Pain may be localized or generalized. Opioids are the treatment of choice, usually on a continuous round-the-clock schedule with additional doses for breakthrough pain at end-stage to provide as much comfort as possible.
   • Spinal Cord Compression in Cancer
     • Definition: compression resulting from direct pressure from the tumor mass or displacement of bony fragments into the spinal canal secondary to vertebral metastases from breast, lung, or prostate (most common).
       • Occurs in5-30% of cancer patients
       • 2nd most frequent complication
       • Affects comfort and function, quality and trajectory of life
     • Symptoms: back pain most common presenting symptom followed by lower motor neuron deficits (hypotonicity, hyperreflexia, paralysis), urinary dysfunction, and constipation
     • Mainstays of treatment (level of treatment will depende on goals of therapy)- dexamethasone, magnetic resonance imaging (MRI) or CT of spine, radiation therapy, and surgical evaluation
2. Nausea/ vomiting: Anti-emetics and /or medical marijuana may help to reduce nausea and vomiting. The patient’s diet should be altered to include those foods the patient can best tolerate, often soft, bland or liquid foods.
3. Dyspnea: Dyspnea is common, and supplementary oxygen may help to provide some relief.
   • Superior Vena Cava Syndrome: A syndrome that develops from the obstruction or compression of the superior vena cava resulting in increased venous pressure and decreased cardiac output. The most common cause is a malignancy present in the mediastinal area (small cell lung cancer)
     • Symptoms: dyspnea (most common), facial and neck swelling, magenta or bluish discoloration of the skin, upper extremity swelling, cough, dilated collateral chest wall veins.
4. Confusion: Supportive care and reorientating the patient may help to reduce confusion, but confusion often persists, especially with high doses of opioids.
5. Bowel/ bladder dysfunction: This is common because of dehydration and opioid use. Stool softeners, laxatives, and encouraging fluid intake may help. If the patient is still able to eat, adding yogurt, fiber, and prune juice to the diet may be helpful.
6. Fatigue

Factors supporting hospice referral:

1. Disease with distant metastases at presentation

OR

2. Progression from an earlier stage of the disease to metastatic disease with either:

• The continued decline despite therapy (like palliative chemo or radiation)

OR

• The patient refuses further disease-related therapy

Certain cancers with poor prognoses, such as small cell lung cancer, brain cancer, and pancreatic cancer, may be hospice eligible without fulfilling the other criteria in this section.

***Poor performance status – a decline in functional status is the most important prognostic indicator and is a measure of how much a patient can do independently.

In the cancer population, performance status is typically measured by ECOG, PPS, or Karnofsky Index.