Introduction to Oncology - Lecture 19

LOs:

1) identify cancer risk factors

2) discuss screening recommendations for specific cancers

3) define terminology used in oncology and chemo

4) define the components and severity for TNM cancer staging

5) explain MOA, indication, and AEs for the meds and therapy categories

6) explain processes that occur during each phase of the cell cycle

7) state equation for body surface area

what is cancer

uncontrolled cell growth, leading to local tissue invasion and eventual metastases to distant locations

risk factors for cancer

-diet

-smoking

-acohol

-weight

-environmental expsure

-age

-biological sex

-genetics

-family hx

what types of cancer can tobacco increase the incidence of?

All cancers. Most notably:

-lung

-renal

-pancreatic

-head and neck

-testicular

How does tobacco increase cancer risk?

-DNA damage

-chronic, low grade inflammation

-accumulation of toxins

-immunosuppression

what types of cancer does alcohol increase the risk of?

Most cancers. Notably:

-breast

-colorectal

-liver

-head and neck

-stomach

how does alcohol increase the risk for cancer?

-acetaldehyde is a carcinogen

-oxidative stress

-increased estrogen levels

name some environmental exposures that can increase cancer risk

-radon

-herbicides

-pesticides

-asbestos

-mustard gas

________ is the single largest source of radiation for almost everyone in WA state

radon

what viruses may cause cancer?

-HPV

-EBV

what types of cancers can HPV cause?

-cervical

-vaginal

-anal

-penile

-oropharyngeal

7 common warning signs of cancer

-change in bowel or bladder habits

-sore throat that does not heal

-unusual bleeding or discharge

-thickening or lump in breast or elsewhere

-indigestion or trouble swallowing

-changes in wart or mole

-nagging cough or hoarseness

best way to reduce cancer incidence or to catch it in early stages

routine screening

explain the recommended cancer screenings, stratified by age

25-39

-cervical cancer screening (25 - 50+)

40-49

-breast

-cervical

-colorectal

-prostate (at 45 yo for AAs)

50+

-breast

-cervical

-colorectal

-prostate

-lung (if smoking hx)

what test is done for breast cancer screening?

What age is it performed at?

How often is it performed?

-mammogram

-40 - 55+ years old

-annually is optional from 40-44

-annually for 45-54

-q2 years for 55+ as long as life expectancy is > 10 years

what is the discrepancy in breast cancer screening?

ACA suggest mammograms start at age 45, but NCCN recommends to start at 40 years old

Don't need to know the above, just know that screening CAN begin at 40, but ABSOLUTELY should begin at 45

what tests are done for colon and rectal cancer?

At what age are they typically performed?

How often are they performed?

age for all is the same:

-40-85 years old

procedures:

-fecal occult blood test (FOBT) yearly

OR

-flexible sigmoidoscopy q 5 years

OR

-colonoscopy q 10 years

what tests are done for prostate cancer?

At what age is this test typically performed?

How often?

Age

≥ 50 years old (optional)

procedure:

Prostate Specific Antigen

frequency:

q1-2 years

-patients may decide to not be screened initially or for follow up, and should be decided with a physician

what test is done for cervical cancer?

At what age does it typically occur?

How often?

test:

Pap

age and frequency:

-21-29 q3 years

-30-65 q 5 years (w/ HPV screening)

-> 65 not tested unless high risk

what test is done for lung cancer?

What age does it typically occur?

How often?

test:

CT

age:

55-74

frequency:

-yearly if meet ALL of:

a) in good health

b) 30 year pack hx

c) still smoke or quit in last 1.5 years

how does cancer metastasize?

-Cancer cells invade blood and lymph, and angiogenesis occurs

-cancer cells attach to vascular endothelium and proliferate at secondary site

what are the letters used in the TNM naming system of cancers, and what do each letter mean?

-T = Tumor

N = Lumph node

M = metastasis

What are the different subclasses of T, N, and M, and what do they mean?

T = Tumor:

T0 - T4

-higher number = larger tumor

N = Lymph node

N0 - N3

-Higher number = more node involvement

M = Metasteses

-M0 = not metastasized

-M1 = Metastasized

Limitation of TNM system

only works for solid tumors. Hematological cancers do not fit this system

what are the different stages of cancer in numerical staging, and what does each one mean?

Stage 0

-carcinoma in situ ("pre cancer")

stage 1

-localized tumor; evidence of growth. Definitely cancer

stage 2

-local spread but still confided to original site

stage 3

-regional spread to nearby organs and/or lymph nodes

stage 4

-distant metastasis

what is neoadjuvant tx

Treatment given before primary tx (surgery) to help shrink tumor:

-chemo or radiation

-AKA induction therapy

what is adjuvant treatment?

Tx given after primary tx (surgery):

-chemo

-sometimes radiation

Main tx options for cancer

-surgery

-radiation

-systemic therapy (chemo, targeted therapy, immunotherapy, alternative medicine)

goal of surgery for cancer

removal of tumor and adjacent lymph nodes

how does radiation therapy treat cancer

damages the tumor (and surrounding tissues)

AEs of radiation therapy

damage to healthy tissue and can cause cancer toxicities in the future

which cancer tx modality tends to be "safest" to the healthy tissues?

systemic therapy treatments (eg/ chemo)

factors that determine effectiveness of a chemotherapy

-heterogeneity

-drug resistance

-pharmacogenomics

-mutations

AEs of chemotherapy

-neutropenia

-anemia

-alopecia

-mucositis

-N/V

-many more

what are the dosing methods used in oncology

-flat dosing

-body surface area

Body surface area equation

How selective are chemotherapy agents

not selective, and treat a wide variety of cancers

significant AE of chemotherapy agents to know

extravascation

what is extravascation

leaking of medication from the vessel, causing blistering, sloughing, and/or necrosis

what to do if extravascation occurs

-stop infusion

-leave needle in for IV access for flushes and antidotes

cisplatin class

alkylating agent

How to treat extravascation from cisplatin

-cold compress 15-20 min q8h x 3d

-sodium thiosulfate

vinblastine class

vinca alkaloid

how to treat extravascation from vinblasine

-Hot compress 15-20 minutes QID x 1-2 d

-hyaluronidase

vinorelbine class

vinca alkaloid

how to treat extravascation from vinorelbine

-Hot compress 15-20 min QID x 1-2 days

-hyaluronidase

Summarize the class and tx of extravascation for:

-cisplatin

-vinblastine

-vinorelbine

cisplatin:

-alkylating agent

-Cold compress 15-20 min q8h x 3 days or sodium thiosulfate

vinblastine:

-vinca alkaloid

-Hot compress 15-20 min QID x 1-2d or hyaluronidase

vinorelbine:

-alkylating agent

-Hot compress 15-20 min QID x 1-2 days or hyaluronidase

what types of medications fall into the class of "targeted therapies" for cancer tx?

-mAbs

-endocrine/hormone therapy

-small molecules

Tamoxifen drug class and MOA

SERM

-blocks estrogen receptor

indications for tamoxifen

-breast cancer

-endometrial cancer

letrozole (Femara) drug class

aromatase inhibitor

-inhibits conversion of androgens to estrogens

in whom do aromatase inhibitors work best?

Post menopausal women, because ovaries are not producing estrogen

indications for letrozole (femara)

breast cancer

Leuprolid (Pupron) drug class and MOA

Gonadotropin Releasing Hormone Agonist (GnRH agonist)

-inhibits gonadotropin secretion

indications for Leuprolide (Lupron)

-prostate cancer

-breast cancer

AEs of the endocrine/hormone cancer therapies (tamoxifen, letrazole, leuprolide)

-hot flashes

-muscle and joint pain

-hypercholesterolemia

which agents are mAbs for cancer?

-rituximab

-trastuzumab

-cetuximab

-bevacizumab

MOA of rituximab (rituxan)

Binds to B-lymphocyte CD20, causing B-cell death

-cytotoxic effects, cell structure effects, apoptosis, and makes cancer more susceptible to other therapies

MOA of Trastuzumab (herceptin)

-monoclonal Ab against HER-2

MOA of cetuximab (erbitux)

EGFR antagonist (Epidermal Growth Factor Receptor Antagonist)

-induces apoptosis and inhibits EGFR production

MOA of bevacizumab

VEGF (vascular endothelial growth factor) inhibitor

-prevents endothelial cells and blood vessels, allowing immune system to kill the cancer

common AEs of mAbs for cancer

infusion rxn:

-flushing

-itching

-SOB

can lead to hospitalization or death

how to attenuate infusion rxn from mAbs used in cancer

pretreat w/ APAP or diphenhydramine

what should be done if an infusion rxn occurs from a mAb?

-stop infusion

-treat reaction

-do not resume until pt is back at baseline

-resume at slower rate and titrate as tolerated

what is a tyrosine kinase

transmembrane receptor that requires extracellular ligand binding, as well as phosphorylation of intracellular binding sites for activation

How do tyrosine kinase inhibitors work for cancer treatment?

inhibit downstream signaling in cell to prevent proliferation or induce apoptosis

which agents are Tyrosine Kinase inhibitors for cancer

-imatinib (gleevec)

-crizotinib (xalkori)

-erlotinib (tarceva)

Imatinib target

BCR-ABL of philadelphia chromosome

target of crizotinib (xalkori)

ALK

target of erlotinib (tarceva)

EGFR

AEs of the TKIs used for cancer

-anemia

-neutropenia

-rash

-edema

-N/V/D

which agents are "immunotherapy" for cancer?

-pembrolizumab (keytruda)

-axicabtagene ciloleucel (Yescarta)

target for pebrolizumab (keytruda)

PD-1

-blocking PD-1 pathway allows activated tumor-specific T cells to kill tumor cells and secrete cytokines to restore anti-tumor immune responses

-essentially "wakes up" the immune system and lets it know a cancer is present

target for axicabtagene ciloleucel (Yescarta)

N/A

how does CAR-T cell therapy work?

T cells are taken from the body and engineered to produce chimeric antigen receptors (CAR)

Reinfused CAR T cells recognize and kill cancer cells

Which medication class is associated with high risk of Acnieform (papulopustular) rash?

EGFR inhibitors

-erlotinib

-cetuximab

A 40 year old male would like to discuss prostate screenings with his primary care provider (PCP). What is the correct age that this patient should start discussing the pros and cons of prostate screenings with his PCP?

50

What is a common side effect of pembrolizumab?

cold sensitivity

What is a common side effect of cisplatin?

a) cardiotoxic

b) N/V

c) hepatotoxic

d) neuropathy

N/V

A patient is diagnosed with cancer that has the following TNM staging: T3 N0 M0. Which of the following is the most accurate description of her tumor?

fairly large, no lymph node involvement, non-metastasized

Which of the following is true regarding adjuvant cancer therapy?

a) Given after primary therapy to prevent recurrence with intent to cure

b) Given before primary therapy to reduce tumor burden/size

c) Given to relieve symptoms but not to cure patient

A

Calculate an ANC for a patient with the following labs:

WBC 1.2 x 103/mL,

Segs 30%,

Bands 10%,

PLT 160,000/mm3,

Hgb 12 gm/dL

480 cells/mL

[WBC x (%Segs + %Bands)] / 100

[1200 x (40)] / 100 = 480

What is the MOA of alectinib?

ALK inhibitor

which agents act against:

-VEGF

-EGFR

-ALK

-BCR ABL

-PD1

VEGF

-bevacizumab

EGFR

-cetuximab

-erlotinib?

ALK

-crizotinib

-alectinib

BCR ABL

-imatinib (gleevec)

PD-1

-pebrolizumab

patient w/ colon cancer has histology testing that reveals malignancy that is EGFR positive. What medication would you recommend as treatment?

cetuximab or erlotinib

what is a common AE for TKIs?

a) polycythemia

b) edema

c) dyspepsia

d) HTN

B) edema