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Cancer Generalities

• Cancer is characterized by uncontrolled cell growth with loss of apoptosis (programmed cell death)
• Can occur in any cell in the body

Types of Cancer

• Leukemia: originates from a blood cell (either myeloid or lymphoid)
• Lymphoma: originates from lymphoid tissue (either in bone marrow or peripheral)
• Myeloma: originates from plasma cells, a type of B cell

Marrow Components

• Neutrophils: can lead to Acute Myeloid Leukemia
• Lymphocytes: can lead to Acute Lymphocytic Leukemia
• Monocytes: can lead to Acute Myeloid Leukemia
• Eosinophils: can lead to Hypereosinophilic Syndrome
• Basophils: can lead to Acute Myeloid Leukemia (seen in CML, also in HD)
• RBCs: can lead to Acute Erythroid Leukemia (rare)
• Platelets: can lead to Acute Megakaryoblastic Leukemia (rare)

Normal Maturation of Neutrophil

• Myeloblast → Promyelocyte → Myelocyte → Metamyelocyte → Band → Neutrophil

Acute Leukemia

• Epidemiology: generally a disease of older people, non-Hispanics, and whites
• Genetic disorders: Down syndrome, Ataxia telangiectasia, Fanconi Anemia, Li Fraumeni
• Radiation exposure and chemical exposure increase risk
• Without treatment, death is inevitable within hours, days, or weeks
• Must be able to identify findings quickly for referral

Signs and Symptoms of Acute Leukemia

• CBC with "BLAST" in the differential (blasts are never normal in peripheral blood)
• Severe fatigue associated with anemia and possible signs of symptomatic anemia
• High white cell count (can be >50-100K, requiring leukapheresis to reduce leukostasis)
• Anemia, fevers, bleeding/bruising, or DIC
• Bone/Joint pains, skin manifestations, pallor, petechiae, and ecchymosis
• Rare: gingival hyperplasia (monocytic), oral candida, herpetic lesions, and CNS involvement

Metabolic/Electrolyte Abnormalities

• Hyperphosphatemia
• Hypocalcemia
• High uric acid
• Hyperkalemia
• High LDH

Why is Acute Leukemia so Dangerous?

• ACUTE Leukemia cells are "sticky"
• Acute leukemia is a MEDICAL EMERGENCY

Treatment of Acute Leukemia

• Always involves chemotherapy (unless palliative care)
• Special case: Acute Promyelocytic Leukemia (APML) aka M3
• Requires immediate treatment with ATRA if suspected
• Auer Rods are specific for and virtually diagnostic of APML

Advanced Treatments

• Bone Marrow Transplant
• Chimeric Antigen Receptor T cell (CART) therapy
• Type of immunotherapy
• FDA approved for: Multiple Myeloma and some B-ALL cases
• Major side effects: fever, Cytokine Release Syndrome (CRS), and long-term B cell aplasia

Leukemias

• Relatives of probands have a 3.5x higher chance of developing lymphoma
• Higher incidence in RA, hemolytic anemia, psoriasis, SLE, Systemic sclerosis, Polyarteritis nodosa, sarcoidosis, Crohn Disease, motor and Celiac disease
• Immunosuppression and viral infections (HIV, HTLV, EBV) are risk factors

Myeloid Leukemias

• Acute: AML (acute myeloid leukemia)
  • Sudden onset
  • >20% blasts
  • Severe symptoms
  • Most common acute leukemia in adults
• Chronic: CML (chronic myeloid leukemia)
  • Philadelphia chromosome translocation BCR-ABL t(9;22)
  • Elevated WBC and platelet count
  • Often normal hemoglobin
  • Always has splenomegaly
  • Can progress to accelerated phase (30% blasts)
  • Treatment: Tyrosine kinases (e.g. imatinib)

Lymphoid Leukemias

• Acute: ALL (acute lymphoid leukemia)
  • Most common in children
• Chronic: CLL (chronic lymphoid leukemia)
  • Affects older people
  • Smudge cells present
  • VERY elevated WBC count (hundreds of thousands)
  • New drugs available in pill form
  • Can have normal life expectancy
  • Increased risk of infections → may benefit from monthly IVIG infusions

Lymphomas

• Hodgkin's Lymphoma
  • Peak incidence at young (20-24) and old (80-84) ages
  • "Owl Eye cells" (Reed-Sternberg cells)
  • Presentation: lymphadenopathy, fatigue, pruritus
  • Treatment: complex chemotherapy, radiation, or combination therapy, BMT, CART
• Non-Hodgkin's Lymphoma
  • Affects all ages, races, and socioeconomic statuses
  • Splenomegaly and implants associated with increased risk
  • Presentation: lymphadenopathy, fever of unknown origin
  • Can be associated with immunodeficiencies and H. pylori infection (MALT tumors)

Plasma Cell Dyscrasias - Multiple Myeloma

• Mild back pain, especially mid-thoracic and when lying down
• Middle-aged individuals affected
• Epidemiology:
  • Higher incidence in African Americans
  • Association with agent orange exposure and family history
  • Increased risk with Body Mass Index
• CRAB criteria:
  • Calcium deviation
  • Renal insufficiency
  • Anemia
  • Bone disease
• Symptoms: throughout the body, blood with cancerous plasma cells and proteins
• Pitfalls:
  • Worsening hypercalcemia (beware dental work 6 weeks before or after)
  • Increased thirst and urination frequency
  • Confusion and bone lesions with pathological fractures
• Referral criteria:
  • Anemia with renal insufficiency +/- hypercalcemia
  • Lytic lesions on imaging
  • Oncologist will risk stratify; consider autologous transplant
• Treatment:
  • Induction chemotherapy followed by maintenance therapy (if ineligible for transplant)
  • Autologous transplant prolongs time to first relapse, but MM is not curable

Myelodysplastic Syndrome (MDS)

• Premalignant disorder that can become cancer if left untreated
• Defined as a pre-malignancy of the bone marrow

Oncologic Emergencies

• Classified into 3 groups:
  • Pressure or obstruction caused by a space-occupying lesion
  • Metabolic or hormonal problems (paraneoplastic syndromes)
  • Treatment-related complications

Mechanical/Obstructive Emergencies

• SVCS (Superior Vena Cava Syndrome)
• MSCC (Metastatic Spinal Cord Compression)
• Pulmonary Embolism
• Urinary Obstruction
• Malignant Effusions

Metabolic or Hormonal Emergencies

• Paraneoplastic Syndromes
  • Due to aberrant tumor production of hormones, peptides, or cytokines
  • Or due to the body's immune attack on normal tissues
• Tumor Lysis Syndrome
  • Tumor bursts due to chemotherapy, leading to metabolic damage
• Hypercalcemia
• SIADH (Syndrome of Inappropriate Antidiuretic Hormone)

Treatment-Related Emergencies

• Neutropenia
• Anemia
• Thrombocytopenia
• Bleeding Disorders
• Clotting disorders

Cancer in the Liver

• Usually metastatic from other organs (e.g. Colon cancer)
• Liver stops making albumin and clots, leading to 3rd spacing into the belly

Paraneoplastic Syndromes

• General problems observed in many patients with advanced or widespread metastatic cancer
• Symptoms resemble those of primary endocrine, dermatologic, rheumatologic, hematologic, or neuromuscular disorders
• Small cell lung cancer (SCLC) is most likely to be associated with paraneoplastic syndromes

Take Home Points

• Patients with cancer can have emergent complications from their disease or treatment
• If a patient presents with a common condition, they have cancer until proven otherwise

Oncologic Emergencies

Superior Vena Cava Syndrome (SVCS)

• SVCS is the clinical manifestation of superior vena cava (SVC) obstruction
• SVC obstruction results in severe reduction in venous return from the head, neck, and upper extremities
• Malignant tumors (lung cancer, lymphoma, metastatic tumors) are responsible for the majority of SVCS cases

Presentation

• Patients with SVCS usually present with neck and facial swelling, dyspnea, and cough
• Other symptoms include hoarseness, tongue swelling, headaches, nasal congestion, epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope, and lethargy
• Bending forward or lying down may aggravate the symptoms
• Characteristic physical findings are dilated neck veins, increased collateral veins, cyanosis, and edema of the face, arms, and chest

Diagnosis and Treatment

• Diagnosis is a clinical one, with a chest radiograph (CXR) as the first step
• CXR findings include widening of the superior mediastinum, usually on the right side
• CT provides the most reliable view of the mediastinal anatomy
• Chemotherapy is effective for small-cell carcinoma of the lung, lymphoma, or germ cell tumor
• Radiation therapy is the primary treatment for SVCS caused by non-small-cell lung cancer and other metastatic solid tumors

Malignant Spinal Cord Compression (MSCC)

• MSCC is defined as compression of the spinal cord and/or cauda equina by an extradural tumor mass
• Thoracic spine is the most common site (70%), followed by lumbosacral spine (20%), and cervical spine (10%)
• Lung cancer is the most common cause
• Most common initial symptom is localized back pain and tenderness
• Pain is exacerbated by movement and coughing or sneezing
• Radicular pain is less common than localized back pain and usually develops later
• Lhermitte's sign may be an early sign of cord compression

Treatment

• Treatment is aimed at relief of pain and restoration/preservation of neurologic function
• Management requires a multidisciplinary approach
• Radiation therapy plus glucocorticoids is the initial treatment of choice for most patients
• The management decision of SCC involves assessment of neurologic (N), oncologic (O), mechanical (M), and systemic factors (S) (NOMS)

Hypercalcemia

• Elevated levels of calcium in the blood (>/10.5 mg/dL)
• Affects 20-30% of patients with cancer at some point during their illness
• Most common cancers causing hypercalcemia are myeloma, breast carcinoma, and NSCLC
• Hypercalcemia is caused by one of three mechanisms: systemic effects of tumor-released proteins, direct osteolysis of bone by tumor, and vitamin D-mediated osteoabsorption

Presentation

• Symptoms and signs can be subtle; more severe symptoms occur with higher levels of hypercalcemia and rapidly rising calcium levels
• Early symptoms include anorexia, nausea, fatigue, constipation, and polyuria
• Later findings may include muscular weakness, hyporeflexia, confusion, psychosis, tremor, and lethargy

Diagnostic Workup

• Calcium level corrected for albumin
• Corrected calcium = measured calcium – measured albumin + 4
• Ionized calcium level is more specific, sensitive, and expensive
• ECG in hypercalcemia often shows a shortening of the QT interval
• Initial workup includes obtaining serum PTH, PTHrP, and calcitriol levels

Treatment

• Emergency management begins with IV 0.9% saline to ensure rehydration with brisk urinary output
• For moderate or severe hypercalcemia, treatment with bisphosphonate is indicated
• Treatment is then directed to control of tumor; reduction of tumor mass usually corrects hypercalcemia

(Febrile) Neutropenia

• Cytotoxic chemotherapeutic agents affect bone marrow function
• The nadir count of each cell type in response to classes of agents is characteristic
• Complications of myelosuppression result from the predictable sequelae of the missing cells' function
• Febrile neutropenia refers to the clinical presentation of fever and

Cancer Definition

• Cancer refers to a wide array of disorders characterized by unregulated cell growth
• Medical and biological term: neoplasm (abnormal tissue that grows rapidly and continues to grow in the absence of the originating growth signal)

Types of Cancer

• Solid tumors: pieces of organ where cells grow out of control and can compress other organs
• Liquid/Hematologic: a disease of the bone marrow, affecting any of the three cell lines (RBC, WBC, Platelets)

Common Cancers

• Top 10 cancers by rates of new cases:
  • Female breast cancer
  • Prostate
  • Lung and bronchus
  • Colon and rectum
  • Corpus and uterus, NOS
  • Melanomas of the skin
  • Urinary bladder
  • Non-Hodgkin lymphoma
  • Kidney and renal pelvis
  • Pancreas
• Top 10 cancers by rates of cancer death:
  • Lung and bronchus
  • Female breast
  • Prostate
  • Colon and rectum
  • Pancreas
  • Liver and intrahepatic bile duct
  • Ovary
  • Leukemias
  • Corpus and uterus, NOS
  • Non-Hodgkin lymphoma

Risk Factors for Cancer

• Tobacco Use:
  • 30% of US cancer deaths related to tobacco use
  • Tobacco risk linked to at least 12 types of cancer
  • 81% of lung cancer deaths attributed to smoking
  • Current rate of adult tobacco use: 14%
• Vaping:
  • Electronic cigarette aerosol can contain harmful substances (nicotine, heavy metals, volatile organic compounds, carcinogenic substances)
  • Vaping among high school students increased from 1.5% in 2011 to 21% in 2018
• Nutrition & Physical Activity:
  • Prudent recommendations to reduce cancer risk:
    • Be physically active
    • Maintain a healthy weight
    • Consume a diet rich in fruits, vegetables, and whole grains
    • Lower consumption of saturated and trans dietary fats
    • Limit alcohol use
    • Avoid excess sun exposure
    • Utilize SPF every day
• Radiation:
  • Individuals exposed to significant radiation doses may increase their lifetime risk of cancer
  • Standardization of CT radiation doses and limiting testing have been important steps in minimizing this risk

Staging

• Staging refers to where a cancer is located and if it has spread from its original source
• TNM system:
  • T: tumor location, size, and level of invasion
  • N: absence or presence and extent of nodal metastases
  • M: absence or presence of systemic metastases
• Cancer spreads to the biggest organ near it
• Once the TNM designations have been determined, an overall “clinical stage” (I, II, III, or IV) is assigned
• IV: metastasis of disease

Oncology Treatment

• Surgery:
  • Tumor removal
  • Debulking surgery
  • Palliative surgery
• Chemotherapy:
  • Systemic chemotherapy
  • Localized chemotherapy
  • Biologic agents
  • Hormonal agents
  • Palliative chemotherapy
• Radiation Therapy:
  • Radiation therapy
  • Stereotactic radiation therapy (Stereotactic radiosurgery)
  • Brachytherapy
  • Palliative radiation therapy

Hospice Care

• Designed to create a 'holding space' for dying persons and their loved ones
• Focuses on providing comfort and support to patients with a terminal illness and a life expectancy of six months or less
• ⅓ of patients die within 7 days of being in hospice
• Challenges a death-denying culture, shifting the medical mindset from "there's nothing more we can do" to "there is much to be done"

Hospice Team and Services

• A circle of care offering expertise and compassion in the service of dying persons' comfort and support of their loved ones
• Plan of care is established and constantly updated to reflect the goals for today
• Services include medical equipment and supplies, related medications, 24-hour on-call, bereavement care, physical therapy, nutritionist, horticultural therapist, music, and respite care

Eligibility and Payment

• Eligibility requires a terminal illness and a life expectancy of six months or less, or choosing comfort care over curative care
• 2 physicians certify that a patient is eligible for hospice care
• Almost 98% of the time, hospice is provided under Medicare Part A or Medicaid, and private insurances often provide a hospice benefit as well

Signs it might be Time for Hospice Care

• Decreased energy
• Less capacity to do daily activities
• Weight loss
• Frequent infections
• More hospitalizations
• More pain
• Failure to thrive

Starting Hospice Care

• Hospice is started by contacting the hospice organization, and they complete the communication with all parties and deem eligibility
• Doctor writes an order for hospice care, and admission visit is set up
• Patient or family signs consents for care, and then it's official

Bereavement Counseling

• Grief support for hospice bereaved and anyone in the community grieving the loss of a loved one
• Services include individual counseling, loss-specific groups, literature, workshops, and memorial services

Other Services

• Kids Path: hospice care, home health, perinatal care, and bereavement services
• CAP-C case management: require shifts of care in home
• Concurrent care: anyone under 18 can still receive chemo, etc.
• Advanced Illness Care Continuum: focuses on quality of life for anyone dealing with serious illness

Palliative Care

• = Comfort Care, focuses on quality of life for anyone dealing with serious illness, at any time, regardless of diagnosis, prognosis, or treatment
• Establishes goals of care, assists with completion of advance directives, and helps navigate complex medical decisions
• Relieves suffering associated with serious illness, and provides timely transfer to hospice when appropriate
• Any diagnosis, any age, and any time in the course of disease can be eligible for palliative care

Centers for Medicare and Medicaid Services Innovation Center

• Building an Improved Dementia Experience (GUIDE) Model: a program variation with a unique team make-up, services, and location