RAT 14, Video 1

What is cancer?

Disease in which cells grow uncontrollably, rapidly, and spread locally or distantly due to genetic mutations

What are proto-oncogenes?

Genes that normally promote cell growth and survival

What happens when proto-oncogenes mutate?

They become oncogenes causing uncontrolled cell growth

What are tumor suppressor genes?

Genes that regulate cell division and promote apoptosis (programmed cell death)

What happens when tumor suppressor genes are inactivated?

Unregulated cell growth and survival of mutated cells

What are DNA repair genes?

Genes that fix DNA replication errors or trigger cell death

What happens when DNA repair genes mutate?

Accumulation of mutations leading to cancer growth

What are the two main cancer groupings?

1. Solid Tumors/Cancer

2. Hematological Cancer/ Malignancies

What is a solid tumor?

A malignant solid mass named by tissue of origin

• Ex: Breast Cancer, Skin Cancer, Colon Cancer, Prostate Cancer

What is a hematologic malignancy?

Cancer originating from blood, bone marrow, or lymphatic system

• Ex: Leukemia, Lymphoma, MM

What are the 6 major cancer classifications?

1. Carcinoma

2. sarcoma

3. myeloma

4. leukemia

5. lymphoma

6. mixed types

What is carcinoma?

Cancer from epithelial cells

• Ex: Breast Cancer, Lung Cancer, Prostate Cancer, Colon Cancer

What is sarcoma?

Cancer from connective tissues like bone or muscle

• Ex: Osteosarcoma (bone), Leiomyosarcoma (smooth muscle), Rhabdomyosarcoma (skeletal muscle)

What is Myeloma?

Cancer from plasma cells origin (produced in BM)

What is leukemia?

Cancer of white blood cells

• often with immature WBC overproduction

What is lymphoma?

Cancer of lymphatic system cells

What is Mixed Types cancer?

Tumors with histological features of a mixture/combo of tissues

• Ex: Carcinosarcoma (carcinoma & sarcoma features)

What is staging?

Extent of cancer spread (size and metastasis)

• usually drives choice of treatment, & may predict prognosis

What is grading?

Describes how abnormal cancer cells look compared to normal cells

What does a low grade prognosis mean?

Tumor cell is similar to original normal cell

• Less aggressive/favorable prognosis

What does a high grade prognosis mean?

Tumor is NOT similar to original normal cell

• More aggressive/unfavorable prognosis

What does TNM stand for?

Tumor size, Node involvement, Metastasis

What does T represent in TNM?

Size/extent of primary tumor

• Numbered 1-4

• Higher # = Larger Tumor

  • Ex. T4 = Largest primary tumor

What does N represent in TNM?

Number/location of Nearby lymph Nodes that have cancer

• Numbered 1-3

• Higher # = More lymph nodes [Ex. N2]

• Number Does NOT necessarily mean exact # of lymph nodes

What does M represent in TNM?

Presence of metastasis or not

• Number 0-1

• 0 = No spread & 1 = Spread

What is ECOG performance status?

Scale measuring patient functional status and ability to tolerate therapy

What does a lower ECOG score indicate?

Better performance status

• Usually indicates better ability to both handle therapy acutely & recover after therapy

What is neoadjuvant therapy?

Treatment before main therapy to shrink tumor

• Ex: Chemotherapy, RT, HT

  • Often referring to solid tumor cancer treatments

What is adjuvant therapy?

Systemic teatment after primary therapy to prevent recurrence

• kill potential remaining cancer cells after the primary/first treatment to lower the risk of cancer coming back

  • Often referring to solid tumor cancer treatments

What is induction chemotherapy?

Systemic and Intense therapy to induce remission

• Often referring to hematological cancer treatments

What is consolidation chemotherapy?

Systemic therapy after remission to prolong survival

• Often referring to hematological cancer treatments

What is maintenance chemotherapy?

Low-dose therapy to maintain remission/prevent relapse

• Often referring to leukemias

What is palliative chemotherapy?

Chemotherapy given to address symptom management &/or shrink the tumor WITHOUT expecting a cure

What is conditioning chemotherapy?

High-dose therapy before stem cell transplant

• Kill off (wipe out) any remaining cancer in the bone marrow, “make room” in the bone marrow for transplant cells to “grow” (engraft), & prevent transplant rejection

  • Referring to hematological cancers eligible for transplant

What is a treatment course?

Plan made of multiple treatment cycles

What is a treatment cycle?

Period of treatment (“round” of therapy) followed by rest

• Usually lasts several months

• Often denoted in the following format: Cycle (“C”) Number (#) & Day (“D”) Number (#) → C1D1

How are chemo regimens often named?

Acronyms of included drugs (using both & generic names)

• Ex: RCHOP 21-Day Cycle X 3 Cycles (Indication: DLBCL - 1st Line Therapy)

  • Rituximab 375mg/m2 IV INF Day 1

  • Cyclophosphamide 750 mg/m2 IV INF Day 1

  • HYDROXYDAUNORUBICIN (Doxorubicin) IV Push Day 1

  • ONCOVIN (Vincristine) IV INF Day 1

  • Prednisone 100mg PO daily Day 1-5

What determines chemo dosing?

• Weight

  • ABW is standardly used unless otherwise directed

    • IBW & AdjBW may be used in specific situations/regimens, including patients with high BMI

• BSA

• fixed dosing

What factors affect dose adjustments?

• Patient performance status (ie. ECOG Score)

• Labs & other testing (ex. SCr, Tbili, ECHO, EKG, etc.)

• Patient age

• Patient tolerability 

• Previously experienced AE(s)

• Intent of therapy (ie. curative, palliative, etc.)

How do you calculate BSA using Mosteller equation?

How do you calculate BSA using Du Bois calculation?

 BSA (m²) = 0.007184 x [Ht (cm)^0.725] x [Wt (kg)^0.425]

• Weight usually in ABW

What is complete response (CR)?

Disappearance of all cancer signs

What is partial response (PR)?

Reduction in tumor size in the body in response to treatment

What is progressive disease (PD)?

Cancer worsening or spreading

What is stable disease (SD)?

Cancer neither growing nor shrinking

What is relapse?

Return of cancer after remission

What is refractory disease?

Cancer resistant to treatment

What is the cell-kill hypothesis?

Each chemo cycle kills a fixed percentage of cancer cells

• hence why multiple treatments are needed to obtain a “cure” &/or get cancer to an undetectable level

How does traditional chemotherapy work?

Targets rapidly dividing cells non-selectively

Why do chemo side effects occur?

Healthy rapidly dividing cells are also affected by therapy

What are common chemo side effect sites?

• GI tract

• hair follicles

• bone marrow

• gametes

What is alopecia in chemotherapy?

Hair loss due to damage to hair follicles

• Occurs ~2-4 weeks into treatment

What is myelosuppression?

Bone marrow suppression → low blood counts

What AE relates to gametes with common traditional chemotherapy?

Infertility

• Fertility-preserving measures prior to treatment (ie. sperm-banking or egg freezing)

What is CTCAE?

System used to grade adverse events severity

A CTCAE score of 1 indicates…

Mild – Asymptomatic or mild symptoms

A CTCAE score of 2 indicates…

Moderate – Symptoms with mild/moderate impairment in daily activity

• Minimal/noninvasive intervention needed

A CTCAE score of 3 indicates…

Severe – Medically significant symptoms with severe impact to daily activity

• Hospitalization/prolonged stay needed

A CTCAE score of 4 indicates…

Life-Threatening

• Urgent intervention needed

A CTCAE score of 5 indicates…

Death related to AE