PAS 601 Intro to Oncology/Approach to Cancer Pt

What is neoplasia?

process of abnormal and uncontrolled growth of cells

What is the product of neoplasia?

neoplasm (tumor)

What are Benign neoplasms?

uterine fibroids and melanocytic nevi (skin moles). They are circumscribed and localized and do not transform into cancer.

What are Potentially malignant neoplasms?

carcinoma in situ. They do not invade and destroy but given enough time, will transform into a cancer

What are Malignant neoplasms?

cancer. They invade and destroy the surrounding tissue, may form metastases and eventually kill the host.

What is a secondary neoplasm?

either a metastatic offshoot of a primary tumor, or an apparently unrelated tumor that increases in frequency following certain cancer treatments such as chemotherapy or radiation therapy

What is the hallmark of cancer?

The deregulation of the

mechanisms controlling

cell cycle progression.

What are the drivers of cancer?

- Proto-oncogenes

- Tumor suppressor genes

- DNA repair genes

involved in normal cell growth and division. However, when these genes are altered or more active than normal, they may become cancer causing genes (or oncogenes) allowing cells to grow and survive when they should not.

proto-oncogenes

What are oncogenes?

cancer causing genes

involved in controlling cell growth and division. Cells with alterations may divide in an uncontrolled manner.

tumor suppressor genes

genes that code for proteins that repair errors. Cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous.

DNA repair genes

What can lead to malignant transformation?

- The formation of novel oncogenes

- The inappropriate over-expression of normal oncogenes

- The under-expression or disabling of tumor suppressor genes

Changes in ________ genes are required to transform a normal cell into a cancer cell.

many

tumor suppressor genes --> nonfunctional proteins

point mutation

large chromosomal regions are deleted leading to loss of genes within those regions

large deletions

a cell gains many copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material.

genomic amplification

two separate chromosomal regions become abnormally fused, often at a characteristic location

translocation

What is an example of translocation?

Philadelphia Chromosome, or translocation of chromosomes 9 and 22

The growth of primary and metastatic tumors requires the recruitment of neighboring:

blood vessels and vascular endothelial cells (EC)

What is angiogenic switch?

the ability of the tumor to promote the formation of new capillaries from pre-existing host vessels

What is tumor angiogenesis?

Formation of blood vessels within a tumor from increase in VEGF

What are angiogenesis inhibitors?

block the growth of blood vessels that support tumor growth rather than blocking the growth of tumor cells themselves

Metastatic cancer is:

cancer that has spread from the place where it first started to another place in the body

What is local invasion in metastasis?

Cancer cells invade nearby normal tissues

What is intravasation in metastasis?

Cancer cells invade and move through the basal membranes of nearby lymph vessels or blood vessels

What is circulation in metastasis?

Cancer cells move through the lymphatic system and the bloodstream to other parts of the body

What is arrest and extravasation in metastasis?

cancer cells arrest, or stop moving, in capillaries at a distant location. They then invade the walls of the capillaries and migrate into the surrounding tissue.

What is proliferation in metastasis?

cancer cells multiply at the distant location to form small tumors known as micrometastases

What is angiogenesis in metastasis?

micrometastases stimulate the growth of new blood vessels to obtain a blood supply for oxygen and nutrients needed for growth

What is the most widely used system for staging?

TNM

What is the TNM staging?

- T = size of primary tumor (TX, T0, Tis, T1-4)

- N = presence of nodal involvement (NX, N0 or N1-3)

- M = presence of metastatic disease (M0 or M1)

What is the second most important determinate of treatment outcome?

performance status

How is performance status evaluated in metastasis?

- Karnofsky

- ECOG

Diagnosis of cancer relies most heavily on:

tissue biopsy

Tumor markers ______ elevated in all people with cancer

are not

Abnormal tumor markers ______ enough to diagnose cancer

is not

What is primary tx?

goal is to completely remove all the cancer or kill the cancer cells (surgery most common)

What is adjuvant therapy?

treatment that is given in addition to the primary treatment to kill any remaining cancer cells or reduce the chance of recurrence (chemotherapy, radiation, hormone therapy are common)

What is neoadjuvant therapy?

treatments used before primary treatment to make the primary treatment more effective

What is radiosensitization?

The use of chemotherapy or other agents that increase the sensitivity of tissue to the effects of radiation therapy, usually by inhibiting cellular repair or increasing the percentage of cells in mitotic phases of the growth cycle.

What does radiation therapy damage?

DNA in the target tissues

What is external beam radiation therapy?

local treatment where beam comes from a machine that aims radiation at the target

What is internal radiation therapy?

the source of radiation is put inside the body; e.g. brachytherapy - solid source where seeds, ribbons, or capsules that contain radiation are placed in the body; e.g. systemic therapy - liquid source or radiation that Is swallowed, IV or injected

Radiation therapy is both ________ and _________

curative; palliative

What is Gamma Knife Radiosurgery?

Beams of highly focused gamma rays to treat small to medium sized lesions in the brain

What type of radiation has minimal effect on surrounding tissue?

Gamma Knife Radiosurgery

What is a stem cell transplant?

Patient receives healthy stem cells to replace their own stem cells that have been destroyed with radiation or high dose chemotherapy

What is Allogeneic stem cell transplant?

cells come from a donor

What is Autologous stem cell transplant?

the cells come from the patient (collected and saved before treatment)

What is Syngeneic stem cell transplant?

stem cells from an identical twin

What is Cord blood stem cell transplant?

cells from umbilical cord blood donated after a baby is born

What does myelosuppression from chemo/radiation lead to?

- neutropenia

- thrombocytopenia

- petechiae & purpura

- anemia

What is the MC side effect of chemotherapy?

nausea with or without vomiting

What is the pathology of CINV?

1.Central pathway: includes the chemoreceptor trigger zone, an area outside of the blood-brain barrier in the medulla oblongata

2.Peripheral pathway: involves the vagal afferent nerves in the GI tract

What is acute CINV?

occurs within the first 24 hours after treatment with a peak at hours 5-6

What is delayed CINV?

manifests between 1-5 days after chemotherapy is given and is associated with agents such as: cisplatin, carboplatin, and cyclophosphamide

What is breakthrough CINV?

N/V that occurs despite preventative antiemetics

What is anticipatory CINV?

occurs before treatment; a conditioned response when a patient has experienced CINV from previous treatments (neural stimulus: smells, colors)

What is refractory CINV?

occurs after chemotherapy despite appropriate use of antiemetic prophylactic and rescue treatments

What is the primary neurotransmitter implicated in acute CINV?

serotonin

What is used to inhibit serotonin in CINV?

5-HT3 receptor antagonists

What are the 5-HT3 receptor antagonists that stop CINV?

dolasetron, granisetron, odansetron, palonosetron

What are the AE of 5-HT3 receptor antagonists?

- QT prolongation

- serotonin syndrome

What is used to inhibit Substance P in CINV?

NK-1 receptor antagonists

What are the NK-1 receptor antagonists used for CINV?

aprepitant, fosaprepitant, rolapitant

What are other drugs used for CINV?

- Olanzapine

- Dexamethasone

- Dopamine Antagonists: (metoclopramide, promethazine, prochloroperazine)

- Cannabinoids: FDA-approved synthetic cannabinoids (dronabinoland nabilone)

- Benzodiazepines

What are antiemetics used for CINV?

- Ondansetron (Zofran)

- Prochlorperazine (Compazine)

- Dexamethasone

- Metoclopramide (Reglan)

- Aprepitant (Emend)

What causes alopecia in chemo/radiation tx?

Anthracyclines, alkylating agents, and topoisomerase inhibitors

What is mucositis from chemo/radiation?

Inflammation of the mucous membranes lining the digestive tract from the mouth to the anus

What are the main complications of mucositis?

pain, infections, and (less commonly) bleeding

Mucositis due to ____________ typically begins 4 to 5 days after the start of therapy, peaks at 10 days, and slowly subsides over the next week

chemotherapy

Mucositis due to __________ usually appears toward the end of the second week of treatment and may last for 6-8 weeks

radiation