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Five leading causes of cancer death in men in US

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lung, prostate, colorectal, pancreas, liver and intrahepatic bile duct

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Five most commonly dx cancers (global)

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lung, breast, colorectal, stomach, prostate

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Most common cancer in men (US)

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Prostate; followed by lung, colorectal, urinary bladder, melanoma of the skin; (global - lung)

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Most common cancer in women (US)

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breast; followed by lung, colorectal, uterine, thyroid

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Five most common causes of cancer death

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lung, stomach, liver, colorectal, breast

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Five most commonly dx cancers (US)

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prostate, breast, lung, colorectal, melanoma of the skin

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Five leading causes of cancer death in women in US

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lung, breast, colorectal, pancreas, ovary

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Cancer survivor statistics: age, female vs male, % with 5 year survival, most common cancer sites in survivors (4)

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59% are 65 or older more women survive then men 64% survive 5 years or more Most common: breast, prostate, colorectal, gynecologic

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Breast cancer LIFESTYLE-related risk factors (3)

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Combined estrogen/progesterone hormone; oral contraceptives, alcohol consumption * Pergonal (fertility drug) increase ovarian cancer risk * White women more likely to develop * oral contraceptives may decrease risk of ovarian and uterine cancers * Alcohol consumption risk for head/neck, liver, colorectal, pancreas, breast, mouth, pharynx, larynx, esophagus, liver

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Cancer incidence has increased due to: (5)

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aging population, tobacco use, exposure to reproductive, dietary, and hormonal risk factors.

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Ethnic group disparities: a. highest incidence of cervical cancer b. highest mortality rate from cervical cancer c. highest incidence and mortality rates of liver and stomach cancer d. highest incidence of breast cancer e. highest mortality rate from breast cancer f. highest incidence and mortality rate of prostate cancer

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a. Hispanic women b. African American women c. Asian and Pacific Islanders d. white women e. African American women f. African American men

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Risk factors and associated cancers: a. HPV-16 b. consumption of red/processed meats c. Hx of DM d. HIV e. Asbestos f. ultraviolet radiation exposure g. Epstein-Barr virus h. steel workers i. rubber workers j. chemical workers k. miners

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a. squamous cell carcinomas of soft palate, tonsils, tongue, cervical cancer b. colorectal, prostate, pancreatic c. pancreatic d. Kaposi sarcoma, B-cell lymphoma e. lung, mesothelioma f. melanoma g. Burkitt lymphoma, nasopharyngeal, undifferentiated parotid carcinoma, Hodgkin, B-cell lymphoma, gastric h. lung cancer i. prostate cancer j. bladder cancer k. gastric cancer and birth defects

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Human viruses and associated cancers: Flaviviruses (HCV)

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Hepatocellular

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Human viruses and associated cancers: Hepadnavirus (HBV)

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Hepatocellular

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Human viruses and associated cancers: Herpes viruses (EBV)

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Burkitt lymphoma, immunoblastic lymphoma, nasopharynageal, Hodgkin, leiomyosarcomas, gastric ca

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Human viruses and associated cancers: Herpes viruses (KSHV)

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Kaposi sarcoma, pulmonary effusion lymphoma, castleman disease

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Human viruses and associated cancers: Papillomaviruses (HPV)

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Anogenital cancers, some upper airway cancers, non-melanoma skin cancer

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Human viruses and associated cancers: Polyomavirus (Merkel cell virus, SV40, JC, BK)

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Merkel cell carcinoma, Brain tumors, non-Hodgkin, mesotheliomas, prostate ca

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Human viruses and associated cancers: Retroviruses (HTLV-1)

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adult t-cell leukemia or lymphoma

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Hepatitis B vaccination for newborns

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three doses: birth, 1-2 months, 6-18 months * associated w/ liver cancer

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Hepatitis A vaccination for newborns

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two doses: 12-23 months, 6-18 months later * hepatitis A not associated w/ increased cancer risk

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HPV vaccination

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Females: routine at 11-12 w/ three doses of Gardasil or Cervarix; 13-26 if not previously vaccinated or not completed three doses Males: 11-12 w/ three doses of Gardasil; 13-26 if not previously vaccinated or not completed three doses, weak immune system, same-sex partner

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American Cancer Society physical activity guidelines

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Adults 150 minutes moderate activity or 75 minutes of vigorous activity / week children: 1 hour per day with vigorous activity 3 days per week Cancer survivors: 150 per week with at least 2 strength training sessions per week

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Secondary prevention

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- measures taken to identify potential for development or existence of a disease in asymptomatic individuals -development of risk profiles and use of screening guidelines - Early detection

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Primary prevention

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- goal is to prevent disease

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Tertiary prevention

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- targets pts with symptoms to slow disease progression and prevent complications - results in decreased mortality and morbidity

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Incidence

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number of new cases identified in a specified population in a defined period

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Prevalence

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- percentage of all individuals with disease at a given point in time in a specified population - includes new and existing - expressed as proportion of disease cases / 100,000

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Mortality rates

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number of disease (cancer) deaths in a population

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Validity

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- accuracy of screening test

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Sensitivity

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- measure of the test's ability to correctly identify persons with the disease (true positives) among the population screened - improved w/ experienced providers conducting and interpreting study - 100% specificity = no false negatives

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Specificity

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- measure of test's ability to correctly identify persons who do not have the disease in the group being screened - 100% specificity = no false positives

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Positive predictive value

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the percentage of persons who screen positive who actually have the disease

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Negative predictive value

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the percentage of persons who screen negative who do not have the disease

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Breast cancer screening guidelines (ACS)

answer

- Women 20-39: CBE q3yrs w/ optional monthly BSE - 40 + years: CBE and Mammography annually - High risk (Life-time risk >15-20%): Annual mammography at age 30; optional MRI screening - mammography when diagnosed with lobular cancer - men with genetic predisposition, baseline mammography at age 40

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Colorectal cancer screening guidelines (ACS)

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Age 50 +: Annual FOBT Plus one of the following: - Flexible sigmoidoscopy every 5 yrs - Double-contrast barium enema q5yrs - CT colonography q5yrs - Colonoscopy q10yrs * required time for polyp to develop into invasive colorectal cancer is 10 yrs * gFOBT only method proven consistently effective * iFOBT superior sensitivity and specificity, not affected by diet or medications

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Facts about CT colonography (5)

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- noninvasive - requires bowel prep - good option for older/frail pts - lower endoscopy w/ bowel prep if lesion detected - insufficient data to recommend as solitary screening test

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PSA results affected by (6)

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- age - BPH - inflammation - Urethral or prostatic trauma - ejaculation w/in 48 hrs - medications: androgen deprivation tx, 5-a-reductase inhibitors, ketoconazole

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Cervical cancer screening guidelines (ACS)

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Between ages 21-29: Pap test q3yrs Ages 30-65: HPV w/ pap test q5yrs or q3yrs w/ pap alone Age >65: regular testing w/ normal results no longer screened Hysterectomy - stop screening unless done to remove cervical cancer or precancerous lesions * generally takes 10-20 years for cervical cancer to develop

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Lung cancer screening guidelines (ACS)

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Age 55-74 (smoking >/= 30 pack years who currently smoke or quit w/in 15 yrs): optional low LDCT; Smoking cessation

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Prostate cancer screening guidelines (ACS)

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- Men w/ 10 yr life expectancy may choose: - Age 50 yrs: PSA w/ or w/o DRE; PSA /= to 2.5 annual testing recommended - High risk w/ African-American ethnicity or father/brother dx with PC before 65 - begin screening at 45, PSA w/ or w/o DRE

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Components of a personal history

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- Demographics - Chief complaint - History of present illness (COLDSPA) - Current medications - Allergies - Past medical hx - Family hx - Social hx - Occupational hx - Review of systems (Gynecologic, breast, endocrine, hematologic/immunologic, musculoskeletal, neurologic)

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Recommendations for genetic testing for colorectal cancer (CRC) (NCI) (5)

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- strong family hx of CRC and/or polyps - personal hx of adenoma or CRC - multiple primary cancers in pt w/ CRC - family hx of other cancers consistent with known syndromes causing an inherited risk of CRC (example: endometrial cancer) - early age of CRC dx (<50 yrs) * slow growing tumor

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Biomarkers

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- substances produced by tumor or body's reaction to cancer - detected in abnormal quantities in blood, body fluids, and tissues - PSA - only marker used in screening - CA 19-9 and CA 125 limited sensitivity and specificity - CA 19-9: GI cancers (colorectal, esophageal), and pancreatic (also elevated in pancreatitis or bile duct obstruction) - CA 125: ovarian cancer; also elevated with uterine fibroids and menstruation - may be present in a variety of benign conditions - not used for screening because they lack specificity

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Tumor marker (Biomarker): Alpha-fetoprotein (AFP)

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Hepatic and germ cell (testicular cancer)

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Tumor marker (Biomarker): Carcinoembroyonic antigen (CEA)

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GI, pancreas, lung, breast

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Tumor marker (Biomarker): Beta-human chorionic gonadotropin (b-HCG)

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Germ cell (testicular cancer)

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Tumor marker (Biomarker): Catecholamine's

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Pheochromocytoma (adrenal medulla)

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Tumor marker (Biomarker): Homovanillic acid/ vanillylmandelic acid (HVA/VMA)

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Neuroblastoma

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Tumor marker (Biomarker): Urinary Bence Jones protein

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Multiple Myeloma

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Tumor marker (Biomarker): Adrenocorticotropic hormone (ACTH)

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Pituitary tumors and benign adenomas

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BRCA 1 and 2 gene mutation screening recommended for: (10)

answer

- multiple cases of early breast cancer in family -strong family hx of other cancers (ovarian, pancreatic) -Ashkenazi Jewish heritage - more than one primary cancer in same person - male breast cancer - individual from family with know positive mutations - triple negative breast cancer - diagnosed at age 45 or younger (early age cancer onset) - diagnosed at age 50 or younger with one or more close relative with breast cancer at age 50 or younger - diagnosed at 50 or younger with more than one close relative with ovarian, fallopian, or primary peritoneal cancer at any age

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Triple negative breast cancer

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(TNBC), the cancer cells do not contain receptors for estrogen, progesterone, or HER2. About 10 - 20 percent of all breast cancers are triple-negative. This type of breast cancer is usually invasive and usually begins in the breast ducts.

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Smaller tumors at dx associated w/ increased survival. Breast cancer risk of nodal metastasis: ? % in tumors less than ? millimeters; ? % in tumors greater that ? mm

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3 % in tumors less than 5 millimeters; 15 % in tumors greater that 5 mm

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Screening test recommended for: (5 cancers)

answer

breast (Imaging - mammography) prostate (Biomarkers or tumor markers - prostate-specific antigen (PSA)) cervical (Cytologic specimen - Pap smear) (has strongest evidence in ability to decrease mortality) lung (Imaging - low-dose computed tomography (LDCT)) colorectal (Chemical assay - fecal occult blood)

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Screening bias (threaten validity of screening test/programs): Lead time bias

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-the appearance of improved survival resulting from longer interval between diagnosis and death

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Screening bias (threaten validity of screening test/programs): Overdiagnosis

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- elderly individual who had undergone screening and has been diagnosed with a slow growing cancer that may have not otherwise been detected and treatment may not be necessary

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Screening bias (threaten validity of screening test/programs): Length time bias

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- a greater proportion of individuals undergoing screening have less aggressive disease -screening more likely to pick up slower growing, less aggressive cancers that have an extended asymptomatic period and can exist in the body longer than fast-growing cancers before symptoms develop

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Screening bias (threaten validity of screening test/programs): Selection bias

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individuals participate in screening programs because they choose to - "select-in" - may be patients with easier access to care, better health habits which may contribute to improved cancer outcomes

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BRCA 1 and 2 gene mutations responsible for: % of hereditary breast cancers % of all breast cancers in women % of all breast cancers in men

answer

20-25% of hereditary breast cancers 5-10% in women 4-40% in men

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Breast Imaging-Reporting and Data System (BI-RADS). Provide uniform reporting schema. Seven categories w/ terminology and follow-up recommendations.

answer

Category 0: additional imaging or comparison with previous mammogram needed Category 1: Negative Category 2: Benign Category 3: Probably benign; Follow-up in short time frame Category 4: Suspicious; biopsy should be considered Category 5: Highly suggestive of malignancy; biopsy strongly recommended Category 6: Known biopsy; proven malignancy

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Definition of cancer:

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a neoplasm characterized by the uncontrolled growth of anaplastic cells that tend to invade surrounding tissue and metastasize to distant body sights.

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Cancer arises from - (3)

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a. multiple mutations in a cell's genes b. genomic instability c. inflammation

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Proto-oncogenes

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- genes that code for proteins involved in normal cell growth. - When mutated, they enable cancer cell to be self-sufficient in growth

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Ras

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- commonly mutated proto-oncogene, especially in pancreatic and colorectal cancer. - Point mutation changes from proto-oncogene to oncogene - normally signals cells to stop proliferating - mutated ras inactivates negative feedback

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Tumor suppressor genes

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- in normal cells control proliferation by preventing uncontrolled growth - When mutated - no longer suppress proliferation - familial cancer syndromes most often associated with

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RB gene

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normally inhibits cell division (stops progression from G1 phase to S phase). mutated in childhood retinoblastoma and many lung, breast, and bone cancers

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"Caretaker" genes

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DNA repair genes that correct mistakes that might be caused by carcinogenes during replication (example: BRCA 1 and BRCA 2 - inherited mutations increase risk of breast, ovarian, and prostate cancer)

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Epigenetics

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- mechanism that may change the activity of a gene w/o changing DNA sequence - factors that do not change DNA but change the way it is translated or expressed in proteins - example: DNA methylation - adding or removing methyl groups from DNA affects the transcription of genes

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Chromosome translocation

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pieces of one chromosome move to another chromosome as the cell divides - example: MYC proto-oncogene normally located on chromosome 8, in Burkitt lymphoma cells it is relocated to chromosome 14 - example: BCR gene normally on chromosome 9 is fused with Abl gene on chromosome 22 in chromic myeloid leukemia (CML) (Philadelphia chromosome)

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Philadelphia chromosome

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- example of chromosome translocation - BCR gene normally on chromosome 9 is fused with Abl gene on chromosome 22 in chromic myeloid leukemia (CML) - makes a protein called tyrosine kinase which promotes the proliferation of myeloid cells

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Rx: Imatinib (Gleevec)

answer

- Targeted tyrosine kinase (Philadelphia chromosome) inhibitor - Treatment of: a. Newly Diagnosed Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML) b. Ph+ CML In Blast Crisis (BC), Accelerated Phase (AP) Or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy c. Adult Patients With Ph+ Acute Lymphoblastic Leukemia (ALL) d. Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) - Dosage: 400-600 mg/day po; or 400mg po bid

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Hereditary non-polyposis colon cancer syndrome (HNPCC) (Lynch syndrome)

answer

- inherited disorder that increases the risk of colorectal cancer, cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, skin, cancer of the ovaries, endometrium - MLH1, MSH2, MSH6, and PMS2, mutations in any of these genes prevent the proper repair of DNA replication mistakes - autosomal dominant

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Tumor necrosis factor (TNF)

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- a cell signaling protein (cytokine) involved in systemic inflammation - endogenous pyrogen - produced chiefly by activated macrophages - primary role regulation of immune cells. - able to induce fever, apoptotic cell death, cachexia, inflammation and to inhibit tumorigenesis and viral replication and respond to sepsis - cytokine that can have an antitumor effect in the process of immune surveillance

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Stroma

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- supportive framework of an organ (or gland or other structure), usually composed of connective tissue - consists of connective tissue, blood vessels, immune inflammatory cells (macrophages and lymphocytes) and associated fibroblasts

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Rx: Cetuximab

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- A recombinant, monoclonal antibody directed against the epidermal growth factor (EGFR) with antineoplastic activity - binds to the extracellular domain of the EGFR, thereby preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization may result in an inhibition in signal transduction and anti-proliferative effects. - may inhibit EGFR-dependent primary tumor growth and metastasis. - blocks lymphangiogenesis (lymphatic spread) - Used in EGFR-+pts to reduce tumor size and inhibit tumor vascularization (angiogenesis) - EGFR is overexpressed on the cell surfaces of various solid tumors - treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer and head and neck cancer. - recommended initial dose is 400 mg/m2; subsequent weekly dose 250 mg/m2 until disease progression or unacceptable toxicity.

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Pleomorphism

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variability in cell size, shape, and nuclei that may be associated w/ cancer development

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Hyperchromatism

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nuclear chromatin more pronounced on staining (Chromatin is a mass of genetic material composed of DNA and proteins that condenses to form chromosomes during eukaryotic cell division)

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Polymorphism

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nucleus enlarged and variable in shape

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Translocation

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- Abnormal chromosome arrangement - exchange of material between chromosomes

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Deletions

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- Abnormal chromosome arrangement - loss of chromosome segments

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Amplification

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- Abnormal chromosome arrangement - increase in the number of copies of a DNA sequence

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Aneuploidy

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- Abnormal chromosome arrangement - abnormal number of chromosomes

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Apoptosis

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- programmed cell death - occurs because of attachment of antibody to antigen - sends complex, multistep signal that causes breakage in cell's DNA - occurs in response to DNA damage

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Contact inhibition

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- process that limits cancer cell growth - cell growth and division stops on physical contact with other cells

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Cell membrane changes unique to cancer cells

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- production of surface enzymes that aid in invasion and metastasis - loss of glycoproteins that aid in cell-to-cell adhesion - Production of abnormal GF receptors - Loss of antigens that label cell as "self" - Production of tumor-associated antigens that mark cell as "non-self"

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Oncofetal antigens

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- expressed by normal cells during fetal development then suppressed - may reappear when cell becomes malignant - examples: a. Carcinoembryonic antigen (CEA) - colorectal, breast, lung, liver, pancreatic, gynecologic b. Alpha-fetoprotein (AFP) - hepatocellular, testicular, lung, pancreatic, and ovarian cancer c. Placental antigens - antigens normally produced by placenta - Human chronic gonadotropin (HCG) - human placental lactogen (HPL): - gynecologic cancers

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Prostate-specific antigen (PSA)

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protein produced by prostate gland; elevated in prostate cancer

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Differentiation antigens

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- found in normal differentiating tissue - elevated in acute lymphocytic leukemia (ALL) chronic lymphocytic leukemia (CLL), and lymphoblastic lymphoma

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Paraneoplastic syndrome

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- rare disorders that are triggered by an altered immune system response to a neoplasm. - nonmetastatic systemic effects that accompany malignant disease. - collections of symptoms that result from substances produced by the tumor - occur remotely from the tumor itself - symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature - simulates more common benign conditions

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Mitotic index

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- proportion of cells in a tissue that are in mitosis at any given time - large # of mitotic cells reflect higher proliferative activity - elevated in cells in GI system, bone marrow, and hair

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Differentiation

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- the extent to which tumor cells resemble comparable normal cells, morphologically and functionally - benign tumors - well-differentiated, resemble tissue of origin - the greater the degree of differentiation, the more likely to have some part of the functional capabilities of normal counterpart - Malignant, undifferentiated, primitive cells

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Tumor grading (4)

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- based on degree to which tumor cells resemble normal counterpart - Grade 1 - Well differentiated - Grade 2 - moderately differentiated - Grade 3 - poorly differentiated - Grade 4 - undifferentiated

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Anaplasia

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- lack of differentiation - result of proliferation of transformed cells that do not mature - more anaplastic, less likely to have specialized function of original cell - disorganization of cells - poorly differentiated, vary in size and shape - nuclei disproportionately large

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Growth fraction

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- the fraction of proliferating cells - varies based on type of tissue and malignancy

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Doubling time

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- time within which the total cancer cell population doubles - influenced by tumor type and vascularity - 30 doublings about the size of a marble, w/ 1 billion cancer cells

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Gompertizan growth curve

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- hypothetical growth curve over the lifetime of an average tumor - at first, tumor growth doubles constantly - growth slows because of hypoxia, decreased nutrients and growth factors, toxins, faulty cell-to-cell communication

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Smallest clinically detectable mass

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1 gram in weight, 1 cubic cm in diameter, one billion cells, or approximately 30 tumor volume-doubling times

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Hyperplasia

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- increase in the number of cells in a tissue - normal: wound healing

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Metaplasia

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- potentially reversible process involving replacement of one mature cell type by another mature cell type not usually found in involved tissue

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Dysplasia

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- alteration in normal adult epithelial cells - loss of uniformity of cells characterized by variation in cell size, shape, organization

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Hallmarks of cancer (biologic capabilities that a cancer cell acquires that transforms a normal cell to a malignant cell) (9)

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- Sustain proliferative signaling - Evade growth suppressors - Resist cell death - enable replicative immortality - induce angiogenesis - have ability to secrete substances such as VEGF's to stimulate angiogenesis - have altered energy metabolism (glycolysis) - evade immune destruction - have high amounts of telomerase, which prevents the telomere segment from shortening, enabling continued cell replication

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Common sites of metastasis: Breast cancer (4)

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Bone, lung, liver, brain

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Common sites of metastasis: Colon (2)

answer

Liver, potentially lungs

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Common sites of metastasis: Colorectal (3)

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Liver, lung, and brain

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Common sites of metastasis: Kidney (4)

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Liver, bone, brain, lungs

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Common sites of metastasis: Lung (4)

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Adrenal gland, liver, bone, and brain

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Common sites of metastasis: Melanoma (skin cancer) (2)

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Lung and brain

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Tumor nomenclature: a. Benign tumors b. Malignant tumors

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a. named by cell of origin with -oma suffix b. named for tissue layer they arise from: 1. mesenchymal origin - sarcomas 2. epithelial origin - carcinomas

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TNM staging system

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T - size or extent of primary tumor N - absence or presence of regional lymph node metastasis M - absence or presence of distant metastases - solid tumors, not liquid (lymphomas and leukemia's)

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Silicosis

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lung fibrosis caused by the inhalation of dust containing silica - associated with Mesothelioma and lung ca

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Epidermolysis bullosa (ep-ih-dur-MOL-uh-sis buhl-LOE-sah)

answer

- a group of rare diseases that cause the skin to blister - blisters may appear in response to minor injury, heat, or friction from rubbing, scratching or adhesive tape. - blisters may occur inside the body, such as the lining of the mouth or intestines - Most types are inherited - has no cure - associated with Squamous cell carcinoma

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Lichen planus (LIE-kun PLAY-nus)

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- an inflammatory condition that can affect the skin, hair, nails and mucous membranes - On the skin, usually appears as purplish, often itchy, flat-topped bumps, developing over several weeks - In the mouth, vagina and other areas covered by a mucous membrane, forms lacy white patches, sometimes with painful sores - associated with oral squamous cell carcinoma

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Lichen sclerosus (LIE-kun skluh-ROW-sus)

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- is an uncommon condition that creates patchy, white skin that's thinner than normal - can affect skin anywhere on your body - most often involves skin of the vulva, foreskin of the penis or skin around the anus - Anyone can get, but postmenopausal women have a high risk - associated w/ vulvar squamous cell carcinoma

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Barrett's esophagus

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- tissue in the esophagus is replaced by tissue similar to the intestinal lining - most often diagnosed in people who have long-term gastroesophageal reflux disease - associated w/ esophageal carcinoma

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Sialadenitis

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an infection of the salivary glands - associated w/ salivary gland carcinoma

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Hashimoto's disease (also known as chronic lymphocytic thyroiditis)

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- a condition in which the immune system attacks the thyroid - resulting inflammation, often leads hypothyroidism

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Sjögren syndrome

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- a systemic chronic inflammatory disorder characterized by lymphocytic infiltrates in exocrine organs - present with, xerophthalmia (dry eyes), xerostomia (dry mouth), and parotid gland enlargement - associated w/ lymphomas

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Squamous-cell carcinoma (SCC)

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- cancer of a kind of epithelial cell, the squamous cell - main part of the epidermis of the skin - one of the major forms of skin cancer. - cells also occur in the lining of the digestive tract, lungs, and other areas of the body

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Marjolin ulcers

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- are malignant tumors arising in chronic wounds - they include carcinomas that transform from the chronic open wounds of pressure sores or burn scars - behave aggressively and have a propensity for local recurrence and lymph node metastases

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Pheochromocytoma

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- rare tumor of adrenal gland tissue - results in the release of too much epinephrine and norepinephrine (hormones that control heart rate, metabolism, and blood pressure) - attacks of raised blood pressure, palpitations, and headache.

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Leiomyosarcoma (LMS)

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- malignant tumors which develop from smooth muscle tissue - Smooth muscle cells make up the involuntary muscles in our body (uterus, lungs, liver, stomach and intestines, walls of all blood vessels, and skin)

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sarcoma

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- cancer of the connective or supportive tissues of the body - include bone, cartilage, fat, muscle, and blood vessels

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Castleman disease AKA: giant lymph node hyperplasia and angiofollicular lymph node hyperplasia

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- rare disorder that involves an overgrowth (proliferation) of cells in lymphatic system - can occur as localized (unicentric) or widespread (multicentric) form.

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Merkel cell carcinoma (AKA: neuroendocrine carcinoma of the skin)

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- rare type of skin cancer that usually appears as a flesh-colored or bluish-red nodule, often on your face, head or neck - most often develops in older people - tends to grow fast and to spread quickly to other parts of your body

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Nowell's theory of clonal evolution

answer

1. clonal cells are cells that can be traced to a single origin 2. have mutations that their lineage a survival advantage or disadvantage 3. with cumulative mutations, characteristics that allow cancer cells to proliferate and spread, may be acquired 4. Different clones may arise from the same tumor and change over time and in response to treatment

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Teratogens

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irreversible, damaging structural malformations in fetuses

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Cancer immunosurveillance

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- host protection process that decreases cancer rates by inhibiting carcinogenesis and preserving cellular homeostasis - immune system can identify and control tumor cells

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Mesenchymal cells

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are able to develop into the tissues of the lymphatic and circulatory systems, as well as connective tissues throughout the body, such as bone and cartilage. A sarcoma is a malignant cancer of mesenchymal cells

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Immunology

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Study of detailed components involved in: the recognition of cellular and tissue changes invasion of microbes development of infections process of malignant tumor growth

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Immune escape

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loss of recognition by cells with in the immune system, which leads to tumor escape and cell proliferation

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Hematopoiesis

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- regulation, production, and development of blood cells - begins with a single cell, a self-renewing pluripotent (capable of giving rise to several different cell types) stem cell - cell divides into undifferentiated hematopoietic stem cell committed to one of two cell lineages: lymphoid or myeloid progenitor cells

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Lymphoid cells (4)

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B cell, helper T cell, killer T cell, natural killer (NK) cells

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Myeloid cells (7)

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dendritic cell, macrophage, neutrophil, eosinophil, mast cell, megakaryocyte, RBC

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Primary lymphoid organs

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- allow for the maturation of lymphocytes, including antigen receptors - Bone marrow - B-cell differentiation and maturation - thymus - T-cel differentiation and maturation

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Secondary lymphoid organs and tissues

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- Sites where foreign antigens encounter lymphocyte immune response - activation of naive B cells and T cells - Waldeyer ring (tonsils and adenoids) - Bronchus - Lymph nodes - initiate immune responses to antigens circulating in the lymph, skin, or mucosal - Spleen - responds to blood borne antigens - Bone marrow - both primary and secondary lymphoid tissue - Lymphoid tissue - GI mucosa and urogenital

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B cells

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- develop in the bone marrow - multiply on recognition of a specific antigen - differentiation into plasma cells which produce immunoglobulins (IgG, IgA, IgM, IgE, IgD)

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T cells

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- migrate to thymus gland - play role in immune surveillance - types of T cells: T helper cells type 1 and 2, T cytotoxic cells

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T helper cells type 1

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- CD4 + cells - secretes cytokines - interact w/ mononuclear phagocytes to assist in their ability to destroy intracellular pathogens

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Cytokine

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any of a number of substances, such as interferon, interleukin, and growth factors, that are secreted by certain cells of the immune system and have an effect on other cells.

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T helper cells type 2

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- CD4 + cells - interacts with B cells, enhancing cell division, differentiation, and antibody production

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T cytotoxic cells

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- CD8 + cells - destroy host cells with the direction of CD4+ cells

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Phagocytes

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internalize and consume pathogenic microorganisms and dibris

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Mononuclear phagocytes

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fixed and mobile phagocytic cells associated w/: blood monocytes: a large phagocytic white blood cell tissue macrophages: a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell

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Polymorphonuclear granulocytes

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- Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm - Also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments - Polymorphonuclear neutrophils (PMNs), Eosinophil, Basophils

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Polymorphonuclear neutrophils (PMNs)

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- 1 of 3 types of polymorphonuclear granulocyte - short lived cell that migrate into tissue (inflammatory response) - engulf and destroy material

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Eosinophil

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- 1 of 3 types of polymorphonuclear granulocyte - attracted to large extracellular parasitic worms - kill by release of contents of intracellular granules - release of histamine and arylsulfatase (an enzyme located in cellular structures called lysosomes) to reduce inflammatory response and granulocyte accumulation

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Basophils

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- 1 of 3 types of polymorphonuclear granulocyte - move to tissue where antigens are present - can create immediate hypersensitivity reactions - similar function to mast cells

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Cellular components of immune system

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1. Cells: Lymphocytes, phagocytes, dendritic cells, null cells, mast cells 2. Mediators of immune system function: complement system, cytokines 3. MHC (major histocompatibility complex)

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Dendritic cells

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- travel from tissue to secondary lymphoid organs to present antigen to T cells -initiate immune responses - function as antigen producing cells for naïve T cells - Used to create Provenge vaccine: dendritic cells exposed to prostatic acid phosphatase (a protein thought to produce tumor response against prostate cancer)

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Null cells

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- express neither T cell nor B cell surface markers - Two types: Natural killer cells and lymphokine-activated killer cells

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Natural killer cells (NK)

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- contain perforin, serine proteases, and other enzymes that create a hole in membrane of cell resulting in cell death - ultimate function: id and destruction of virus-infected cells and certain tumor cells

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Perforin

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a protein, released by killer cells of the immune system, that destroys targeted cells by creating lesions like pores in their membranes.

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Lymphokine-activated killer cells (LAK)

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- produced when lymphocytes removed from blood and cultured with IL-2 or alloantigens - crates cytotoxicity in targeted cells

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Mast cells

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- ganulocytes w/ multiple mediators that produce inflammatory response within tissues - contain receptors on surface that bind to Fc region on IgE antibodies, leading to cellular degradation - Two kinds: mucosal and connective tissue mast cell

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Complement system

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- mediator of immune system function - an interactive network of approximately 20 unique serum and cell proteins - three pathways: Classical, lectin, and alternative - functions: Mast cell degranulation, leukocyte chemotaxis, opsonization, cell lysis

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Complement cascade: Classical pathway

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- acquired immunity - activated by antigen-antibody complexes

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Complement cascade: Lectin pathway

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- activated by specific bacterial cabohydrats

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Complement cascade: Alternative pathway

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- activated by gram negative bacteria and fungal polysaccharides

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Opsonization

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phagocytosis of antigen-antibody complexes when products of the complement cascade interact with neutrophils and macrophages

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Cytokines

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- molecules that enhance communication and induce growth and differentiation of lymphocytes and other cells within the immune and neuroendocrine system - 5 cytokines: IFNs, ILs, Hematopoietic growth factors, tumor necrosis factors, chemokines

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Interferons (IFNs)

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- a group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells - first line of viral resistance

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interleukins (ILs)

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- a class of glycoproteins produced by leukocytes for regulating immune responses - produced mainly by T cells

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Hematopoietic growth factor

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- guide and direct cell division and differentiation of bone marrow stem cells and leukocytes - a group of glycoproteins that causes blood cells to grow and mature

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Tumor necrosis factors (TNF)

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- mediate inflammation and cytotoxic reactions - a cell signaling protein (cytokine) involved in systemic inflammation - one of the cytokines that make up the acute phase reaction

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Chemokines

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- guide leukocyte movement around body between blood and tissue - activate cells to perform specialized immunologic funciton - a class of cytokines with functions that include attracting white blood cells to sites of infection

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Major histocompatibility complex (MHC)

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- a set of cell surface proteins essential for the acquired immune system to recognize foreign molecules, which in turn determines histocompatibility - main function is to bind to peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells - mediate interactions of leukocytes with other leukocytes or with body cells - determines compatibility of donors for organ transplant, as well as one's susceptibility to an autoimmune disease - also called the human leukocyte antigen (HLA)

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Natural immunity barriers (3)

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- present at birth to prevent damage by environmental substances and thwart infection - Physical - Mechanical - Biochemical

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Inflammatory response

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rapid activation of plasma protein systems, mast cell degranulation, vascular changes, and influx of leukocytes

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Acquired immunity

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- reacts to specific molecules - slower to respond - has "memory" - longer lived than innate response

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Humoral immunity

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- B cell immunity - wait for macrophages to bring antigens to them for processing in lymphoid tissue - each B cell lymphocyte recognizes only one type antigen (specificity)

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Immune effector mechanisms (4)

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- antibodies (immunoglobulins) protect body from antigens and cells containing them by direct action via: - neutralization - antibody-dependent-cell-mediated cytotoxicity - complement-dependent cytotoxicity - apoptosis

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Antibody-dependent-cell-mediated cytotoxicity

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- is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies. - usually mediated by IgG. - occurs when antibody binds to antigen and forms a bridge to cause direct cell kill - Immunoglobulins, NK cells, and macrophages participate

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Neutralization

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- an antibody that defends a cell from an antigen or infectious body by neutralizing any effect it has biologically example: diphtheria antitoxin, which can neutralize the biological effects of diphtheria toxin -occurs when cell growth is stopped because of interference of immunoglobulin with antigen

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Complement-dependent cytotoxicity

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- immune process by which the antibody-antigen complex activates a cascade of proteolytic enzymes that ultimately results in the formation of a terminal lytic complex that is inserted into a cell membrane, resulting in lysis and cell death - activated via "classical pathway"

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Classical pathway

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- the activation of complement by an antigen-antibody reaction. - Compare alternative pathway

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Alternative pathway

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- the activation of complement by contact with polysaccharides on bacteria, protozoa, or yeast cells: a nonspecific immune response. - Compare classical pathway

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Cell-mediated immunity

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- T-cell immunity - Antigen presented to T lymphocytes by macrophages via antigen-presenting cell (APCs) - T lymphocytes specific to presented antigen are produced (activated T cells) - T lymphocyte memory cells produced and respond by activating T lymphocytes when exposed to same antigen - cytotoxic T cells and NK cells capable of directly attacking other cells and destroying them - T lymphocytes able to recognize and bind to antigens - T lymphocytes cannot read epitopes until molecules is phagocytized and digested and antigens linked with MHC antigens on surface of NK T lymphocytes.

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Antigen-presenting cell

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- a cell that displays antigen complexed with major histocompatibility complexes on their surfaces - this process is known as antigen presentation - T cells may recognize these complexes using their T cell receptors - These cells process antigens and present them to T-cells.

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Physical, mechanical, and biochemical barriers to prevent damage by environmental substances and thwart infection

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- Physical: epithelial cells of skin and mucus membranes - Mechanical: sneezing, coughing - Biochemical: mucus, saliva, earwax

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Tissue associated antigens (TAAs)

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- occur when cell transitions from normal to malignant - Examples: HER2, carcinoembryonic antigen, CA-125, PSA

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Passive immunity

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- the transfer of antibodies from an immunized individual to a nonimmunized individual - example: the transfer of antibodies across the placenta from mother to infant

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Active immunity

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results from development of antibodies in response to an antigen such as from vaccination

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Agglutination

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- result of the complement cascade - products make the outer coating of invading cells sticky - can change the structure of some viruses, making them non-virulent

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Pemphigus

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- an autoimmune disorder in which the immune system produces antibodies against specific proteins in the skin and mucous membranes - a skin disease in which watery blisters form on the skin

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Rx: Rituximab

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- Treatment of: Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL) - is not chemotherapy; a type of antibody therapy - targets and attaches to the CD20 protein found on the surface of blood cells with cancer. - Once attached, works in 2 different ways: 1. By helping your own immune system destroy the cancer cells 2. By destroying the cancer cells on its own

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Chromosomes

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- threadlike structures that contain genetic information - 46 chromosomes in human body; 23 chromosome pairs - small arm "p"; large arm "q" - Autosomes: 22 chromosome pairs; do not determine sex - Sex chromosome: X and Y; Women two X, Men one X and one Y

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Nucleic acid

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- Macromolecules containing hydrogen, oxygen, nitrogen, carbon, and phosphorus - serves as a blueprint for proteins and, through the actions of proteins, for all cellular activities - The two types are DNA and RNA.

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Deoxyribonucleic acid (DNA)

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- comprises two nucleotide chains, running in opposite directions, held together by hydrogen bonds, coiled to form double helix - Two types of nitrogenous bases present: 1. purines: adenine (A) and guanine (G) 2. pyrimidines: thymine (T) and cytosine (C) - A attaches to T; G attaches to C - Base pairs are complementary of the double strand - contains the sugar deoxyribose - provides instruction for making proteins - provides hereditary information

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Ribonucleic acid (RNA)

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- Single strand chain which represents a complimentary copy of a strand of DNA - created in the process of transcription - Two types of nitrogenous bases: 1. purines: adenine (A) and guanine (G) 2. pyrimidines: uracil (U) and cytosine (C) - nucleic acid containing the sugar ribose - The class of nucleic acids that comprises messenger RNA, ribosomal RNA, and transfer RNA - travels from the nucleus to the cytoplasm of the cell, carrying the coded message that directs the formation of specific proteins

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Transcription

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- process of making RNA from DNA

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Translation

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- process of making proteins (chains of amino acids) from RNA - genetic information coded in mRNA directs the formation of a specific protein at a ribosome in the cytoplasm

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Messenger RNA (mRNA)

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- contains information about the order of the amino acids in a protein - leaves the nucleus and goes to the ribosome for translation - read in sets of 3 nucleotides called codons

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Codon

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- a chain of three mRNA nucleotides that specifies production of one of 20 different amino acids - more than one codon will code for a specific amino acid - change in 3rd place of codon rarely causes amino acid change - change in 1st place will cause different amino acid to be produced - three "stop" codons stop growth of amino acid: transfer RNA, ribosomal RNA, and several small silencing RNAs

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Transfer RNA (tRNA)

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- brings amino acids to site of protein synthesis

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Ribosomal RNA (rRNA)

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- provides structural support for protein in addition to other functions

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Gene

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- individual units of hereditary information, located at specific position on chromosome - consit of a sequence of DNA that codes for a specific protein - consist of exons and introns: 1. exons - protein coding segments 2. introns- non protein coding segments

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Types of genetic mutation ( disease-causing variations in the sequence of DNA) (6)

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1. Frameshift: one or more bases added or deleted 2. Missense: single base pair changes that result in the substitution of one amino acid for another in the protein being constructed 3. Nonsense: change in amino acid signal into a stop 4. RNA negative: the absence of RNA 5. Splicing: DNA that should be removed is retained or DNA that should not be added is spliced in 6. Polymorphisms: not disease related; occur at variable frequency; associated with individualization of population

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Chromosomal abnormalities (4)

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1. Translocation: segments of one chromosome break off and attach to other chromosome; result in altered protein production 2. Aneuploidy: abnormal # of chromosomes 3. Loss of heterozygosity: loss of a segment of both copies of a chromosome 4. Microsatellite instability: repetitive pieces of DNA scattered throughout genome in noncoding regions (introns)

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Lynch Syndrome

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- Previously known as hereditary nonpolyposis colorectal cancer - inherited condition - increased risk of developing colorectal, endometrial, gastric, ovarian, sm bowel, pancreatic, urinary tract, kidney, bile duct, certain skin tumors (sebaceous adenomas), and brain tumors. - average age for colorectal cancer to be diagnosed is 45, compared with the average age of 72 - genes identified that are linked to include MLH1, MSH2, MSH6, PMS2, and EPCAM. - follows an autosomal dominant inheritance pattern - Approximately 3% to 5% of all cases of colorectal cancer are thought to be due to

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Types of regulatory genes (3):

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1. Proto-oncogene: normal cell growth and regulation; mutation to oncogene result in uncontrolled cell division 2. Tumor suppressor gene: cell cycle regulation and DNA repair; mutation develop uncontrolled cell growth 3. DNA repair gene: a. mismatch repair: keep DNA free of changes during DNA synthesis; associated w/ microsatellite instability in Lynch Syndrome

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Telomerase

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- plays role in cellular aging - repressed as cells age resulting in telomeres (end of chromosomes) lost - reactivated in cancer, resulting in intact telomeres, facilitating cell immortalization

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Pharmacogenetics

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- identifies the genetic basis for differences in metabolism of an agent and associated response - used to individualize therapy - drugs designed specifically for the genetic characteristics of a tumor

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Pharmacodynamics

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study of the biochemical and physiologic effects of durgs on body

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Pharmacokinetics

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description of how the body absorbs, distributes, metabolizes and excretes a drug

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Features of hereditary cancer (7)

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1. family member with known germline nutation 2. early age of onset 3. cancer of rare histology 4. cancer in two of more close relatives 5. Bilateral cancer in paired organs 6. Multiple primary cancers in single individual 7. constellation of cancers in family of know hereditary cancer syndrome

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Penetrance

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- the proportion of all individuals w/ a specific genotype that express the specific trait - the cancer risks associated with a specific genetic mutation, determined by weather the corresponding phenotype is expressed

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Expression

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the degree to which a single individual w/ a specific genotype will exhibit a specific trait

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The Health Insurance Portability and Accountability Act (HIPAA)

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-genetic information cannot be used as a preexisting condition or to determine eligibility for insurance

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The Genetic Information Nondiscrimination Act (GINA)

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- health insurance and employment discrimination based on genetic information

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Autosome

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- Any chromosome that is not a sex chromosome - 22 chromosome pairs that do not determine gender - each parent contributes half of each pair

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Chromosome

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- A threadlike, gene-carrying structure found in the nucleus. - Each chromosome consists of one very long DNA molecule and associated proteins. - have genes located at specific positions; each gene contains genetic information

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Gene mutations and correlated cancers: - p53 - PTEN - BRCA1 - APC - MSH2 - BRCA2

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- p53: breast and brain, leukemia's, sarcomas, adrenal cortical tumors - PTEN: breast, thyroid (follicular type), endometrium, benign skin lesions - BRCA1: breast, ovarian - APC: colon, rectal, colon polyposis (adenomas), other desmoid tumors (tumor in the fibrous (connective) tissue of the body that forms tendons and ligaments) - MSH2: colon, ovary, endometrium -BRCA2: malignant melanoma, ovarian, fallopian tube, pancreatic

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Three types of regulatory genes:

answer

1. Tumor suppressor gene 2. Proto-oncogene 3. Mismatch repair gene (correct DNA replication errors)

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Pharmacogenomics

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- identifies genetic differences that influence cancer treatment - Example: role of DPD (decision peptide driver) protein in the inactivation of active 5FU

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Pharmacogenomic testing required for:

answer

Vemurafenib for melanoma Cetuximab and Panitumumab for colon cancer Exemestane, Fluvestrant, Letrozole for breast cancer Dasatinib for colon cancer Trastuzumab and Lapatinib for breast cancer Imatinib for CML and MDS Tyrosine kinase inhibitors for gastrointestinal stromal tumors

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Phase one clinical trials

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- evaluate safety and tolerability - Determine maximum tolerated dose - Determine dose limiting toxicity - Define optimal biologically active dose - Evaluate pharmacokinetic and pharmacodynamics - Observe preliminary response

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Phase two A and B clinical trials

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IIA - Demonstrate activity of intervention - Establish proof of concept IIB - establish optimal dosing - evaluate safety

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Phase three clinical trials (Randomized controlled trial)

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- compare efficacy of intervention being studied to control group - evaluate safety

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Phase Four (post marketing study)

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- evaluate safety - compare to similar product already on market - monitor for long-term and additional safety, efficacy, and QOL - assess drug-food interactions - assess effect in specific populations - determine cost effectiveness - involves agents that have been already tested and approved by the FDA for use in clinical setting.

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Observational study vs interventional study

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- Observational: researcher is assessing or describing biomedical and health outcomes in human subjects; focus is not on changing outcome for subjects - Interventional: involves some type of an intervention or interventions that will be evaluated

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Comparative Effectiveness Research

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the process of generating, synthesizing, and comparing the benefit and harm of interventions in typical patients to identify the most efficacious, safe, and cost-effective care for an individual.

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Two main types of breast cancer in situ:

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1. Ductal carcinoma in situ (DCIS) - noninvasive involving duct cells; 85% of in situ cases 2. Lobular carcinoma (LCIS) - involves milk-producing lobule cells; Pleomorphic LCIS - aggressive variant, more likely to develop into invasive lobular carcinoma

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Breast cancer: Ductal carcinoma in situ (DCIS)

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- nonmalignant, intraductal carcinoma - proliferation of cells inside ducts - staged as stage 0 - may become invasive, excision recommended - non palpable, detected by mammography and pleomorphic calcifications (broken glass dispersal pattern of calcifications)

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Breast cancer: Lobular carcinoma in situ (LCIS)

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- lobular neoplasia - multicentric (more than one tumor) - multifocal (involves more than one quadrant of breast) - usually an incidental finding - staged as stage 0 - excision recommended

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Risk factors for breast cancer: (15)

answer

- Female - ; 55 yo (75% of all cancers) - 1 in 8 white women; 1 in 10 African American - Early menarche - late age of first pregnancy (;30 yo) - Nulliparity - Never breast fed - Use of hormone replacement tx - Post thoracic Rtx - Family history - Genetic mutation - High fat diet - Obesity - Alcohol - Smoking

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Hereditary breast cancer syndromes: (10) 5-10% of female cancers; 4-40% of male cancers

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- BRCA 1: located on chromosome 17q21; accounts for 20% of all familial breast cancers; 50-85% lifetime risk; 15-45% chance of ovarian cancer - BRCA 2: Located on chromosome 13q12; lifetime risk 80%; increased risk of breast, pancreatic, melanoma, and ovarian - TP53 (tumor protein 53): LiFraumeni syndrome - ATM (ataxia telangiectasia mutated): ataxia-telangiectasia disease - PTEN: Cowden disease; lifetime risk 25-50% - STK11/LKB: Peutz-Jeghers syndrome - CHEK2 - Lynch Syndrome: hereditary nonpolyposis colorectal cancer - PALB2 - BRIP1

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Prevention of breast cancer:

answer

- Tamoxifen (Nolvadex) - Raloxifene (Evista) - Aromatase inhibitors (exemestane)

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Tamoxifen (Nolvadex):

answer

- 1st generation selective estrogen receptor modulator (SERM) - 49% overall reduction of breast cancer - SE: Hot flashes, cognitive changes, increased triglyceride levels, thromboembolism, endometrial cancer

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Raloxifene (Evista)

answer

- 2nd generation SERM (selective estrogen receptor modulator) - approved for reduction of Breast cancer risk in postmenopausal women and tx of osteoporosis - SE: Hot flashes, leg cramps, arthralgias, HA, flu like symptoms

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Aromatase inhibitors

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- group of drugs designed to reduce estrogen - blocks conversion to active estrogen/androgen/corticosteroid/mineralocorticoid to reduce cell growth in breast, prostate and/or adrenal cancer. - Exemestane SE: hot flashes, HA, vaginal bleeding, joint pain, bone loss

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Histopathologic classifications of breast cancers: (8)

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- Ductal adenocarcinoma - Lobular carcionoma - Inflammatory - Paget disease of the breast - Cystosarcoma phyllodes - Special subtypes - Rare tumors - Nonmalignant tumors (Ductal carcinoma in situ, Lobular carcinoma in situ)

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Breast cancer: Ductal adenocarcinoma

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- 70-80% of cases - Invasive ductal carcinoma (IDC) most common - Clinical prognosis depends on cellular morphologic characteristics: ER, PR, Ki67 (marker of cell proliferation) and Her2/neu

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Breast cancer: Lobular carcinoma

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- 10-15% of cases - Invasive lobular carcinoma (ILC): capable of metastasis - Radial pattern of spread, not easily detected on mammography, non-palpable, more like to affect bilateral breast compared w/ IDC (Invasive ductal carcinoma)

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Common sites of breast cancer metastasizes: (6) Distant metastatic sites

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- pericardium - abdomen - ovary - uterus - stomach - eye

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Inflammatory breast cancer

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- 1% of cases - Aggressive - dermolymphatic invasion with erythema, mimics mastitis - edema in skin (peau d'orange) with palpable border

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Five subgroups of breast cancer:

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1. Luminal A tumors - highest levels of ER (estrogen receptor) expression; ER+, PR+ (progesterone-receptor), HER2- 2. Luminal B tumors - ER+, PR-, HER2+ 3. Normal-like breast tumors 4. Her2-amplified - amplification of HER2 gene on chromosome 17 5. Basal tumors - triple negative

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BRCA-1 gene mutation

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- located on chromosome 17q21 - accounts for 20% of all familial breast cancers - 50-85% lifetime risk - men increased risk of developing prostate cancer

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Breast cancer: Oncotype DX

answer

- 21 gene assay used to predict chemo benefit and estimate 10 year risk of distant recurrence in women with early stage, node-negative, estrogen receptor-positive invasive breast cancer - score determined from gene expression: 0-17 low risk; 18-31 intermediate risk; >31 high risk

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Breast cancer: Bloom Richardson grading system

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- determine histologic grading of breast cancer - Criteria: 1. nuclear grade evaluation of the size and shape of the nucleus of the tumor cells 2. the mitotic rate (how many dividing cells are present) 3. ductal structure (the amount of tubular formation in the breast cancer tissue)

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Breast Cancer subgroup: Luminal A tumors

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1. ER+, PR+, HER2- 2. tend to be low grade 3. Respond to endocrine tx, favorable prognosis 4. less responsive to chemotherapy

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Breast Cancer subgroup: Luminal B tumors

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1. ER+, PR-, HER2+ 2. Prognosis worse than Luminal A 3. Tend to be high grade 4. may benefit from chemo and targeted HER2 tx

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Breast Cancer subgroup: Normal-like breast tumors

answer

1. Gene expression similar to normal breast epithelium 2. Prognosis similar to luminal B tumors

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Breast Cancer subgroup: HER2-amplified

answer

1. amplification of HER2 gene on chromosome 17 2. Decrease expression of ER and PR 3. upregulation of vascular endothelium growth factor (VEGF) 4. Tx: trastuzumab (Herceptin)

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Breast Cancer subgroup: Basal tumors

answer

1. Triple negative, not responsive to hormonal therapies 2. poor prognosis 3. treated w/ combination surgery, chemotherapy, radiation

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Breast cancer: histologic grade (3)

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Grade 1: low grade, well differentiated Grade 2: intermediate grade, moderately differentiated Grade 3: high grade, poorly differentiated

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Breast Cancer: Metastatic pattern Most common organs involved in metastases: (5)

answer

1. regional lymph nodes (axillary, internal mammary, inferior, supraclavicular) 2. Contralateral breast: invasive lobular carcinomas 3. Distant metastatic sites: bone, skin, lung, liver, abdomen, eyes, bladder, brain, and spinal cord 4. Hematogenous spread: liver, lung, bone, brain, abdomen 5. Lymphatic spread: intramammary lymph nodes, axillary nodes, mediastinal nodes, lymphatics

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Breast Cancer: factors affecting prognosis and tx (8)

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1. Lymph node status 2. Tumor size 3. Histologic grade 4. Hormone receptor status 5. Histologic tumor type 6. Ki-67 proliferation rate 7. Oncogene HER2/neu and EGFR overexpression 8. Breast cancer assay - Oncotype DX or MammaPrint

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Breast Cancer: Ki-67 proliferation rate

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Ki-67 is a protein in cells that increases as they prepare to divide. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are the more quickly they are dividing. 20% high

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Breast Cancer: Staging

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T: Primary tumor size (15: TX to T4d) N: regional lymph node involvement (10: NX to N3c) M: Distant metastasis (3: M0, cM0(i+), M1) Anatomic stage: Stage 0 - Stage IV

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Breast Cancer: Treatment: Clinical stage I, IIA, or IIB or T3 N1 M0 (4)

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Locoregional tx: 1. Lumpectomy w/ radiation and possible chemo, antihormonal tx, and antibody tx 2. Total mastectomy w/ axillary staging; Chemo and radiation w/ close margins, positive margins, and/or positive lymph nodes 3. Sentinel lymph node biopsy (most likely first lymph nodes to which cancer ma spread) 4. Axillary lymph node dissection

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Breast Cancer: Treatment: ER- and or PR positive (Premenopausal vs Post)

answer

1. Adjuvant endocrine tx a. Premenopausal: Tamoxifen for 5 yrs w/ or w/o ovarian suppression b. Postmenopausal: Aromatase inhibitor for 5 yrs

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Breast Cancer: Treatment: HER2 positive (4)

answer

1. Trastuzumab (Herceptin)- monoclonal antibody 2. Lapatinib (Tykerb)- kinase inhibitor; used w/ metastatic HER2-positive in combination w/ chemo 3. Pertuzumab (Perjeta) - monoclonal antibody 4. TDM-1 - antibody w/ trastuzumab (Herceptin) and mertansine (DMI)

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Breast Cancer: Treatment: Non-trastuzumab (Herceptin) containing : locally advanced and metastatic disease (4)

answer

1. TAC: docetaxel, doxorubicin, cyclophosphamide 2. Dose dense AC: doxorubicin and cyclophosphamide followed by paclitaxel q2 wks 3. AC: doxorubicin and cyclophosphamide followed by weekly paclitaxel 4. TC: docetaxel and cyclophosphamide

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Breast Cancer: Treatment: trastuzumab (Herceptin) containing : locally advanced and metastatic disease (3)

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1. AC followed by T plus concurrent trastuzumab (doxorubicin and cyclophosphamide followed by paclitaxel plus trastuzumab) 2. TCH (docetaxel, carboplatin, trastuzumab) 3. Traztuzumab, pertuzumab, and docetaxel

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Chemotherapy: Tamoxifen (Potential SE) (6)

answer

Hot flashes, uterine ca, DVT, vaginal discharge, increased bone density, depression

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Chemotherapy: Aromatase inhibitor

answer

1. blocks enzyme aromatase preventing conversion 1. blocks enzyme aromatase preventing conversion of androgens (adrenal gland hormones) to estrogen. Estrogen dependent tumors will shrink. 2. Example: anastrazole, exemestane, letrozole 3. Potential SE: hot flashes, joint aches, bone density loss, dry skin, vaginal dryness, and deceased libido 4. used in patients who are postmenopausal at dx and are hormone receptor positive 5. used to reduce likelihood of disease recurrence 6. usually given for 5 year time

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Chemotherapy: Trastuzumab (Herceptin) (Potential SE) (4)

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1. monoclonal antibody 2. Potential SE: allergic reaction, decreased left ejection fraction, pulmonary toxicity w/ interstitial pneumonitis, pulmonary fibrosis

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Chemotherapy: Lapatinib (Tykerb)

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1. kinase inhibitor 2. metastatic HER2 + 3. used in combination w/ chemo 4. recommended dose 1250 mg po dly 5. 1 hr before or after meal 6. Potential SE: decreased left ejection fraction, hepatic toxic, N, V, D, interstitial lung disease or pneumonitis, Q-T interval prolongation, palmar and planter erythrodysesthesia, rash, fatigue

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Lung Cancer: Common sites of systematic spread (4)

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Brain, liver, adrenal glands, and bone

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Lung Cancer: Paraneoplastic syndromes and oncologic emergencies associated w/ (6)

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- Hyper calcemia - SIADH - Spinal cord compression (SCC) - Superior vena cava syndrome (SVC) - Cardiac tamponade - Uncontrolled pain

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Lung Cancer: Two major types of lung cancer

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- Non-small cell (NSCLC) (85%) - Small cell (SCLC)

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Lung Cancer: Staging: NSCLC vs SCLC

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- TNM - NSCLC: I-III a and b or IV w/ occult; Stage 0 also identified - -SCLC: limited (confined to one lung and lymph nodes on same side) or extensive (spread widely in lung to other lung, distant organs (2/3's diagnosed as))

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Lung Cancer: Histology (3)

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- Squamous cell carcinoma (uncontrolled multiplication of cells of epithelium) - Adenocarcinoma (neoplasia of epithelial tissue that has glandular origin) approx. 80% of lung cancers - Large cell carcinoma: approx. 5-10%, dx of exclusion (not SCC, squamous cell, or adenocarcinoma)

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Lung Cancer: pack history

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Number of packs of cigarettes a day multiplied by number of years

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Lung Cancer: Screening guidelines

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- ;30 pack years or ;15 year quit, healthy, age 55-74 - Annual screening w/ low dose chest CT

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Lung Cancer: NSCLC Treatment

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1. Surgery - best option for cure; primary tx for early stage NSCLC (stages I and II) 2. Radiation - adjuvant and/or palliation 3. Chemotherapy- cisplatin based doublet 4. Targeted therapy- EGRF and/or ALK positive

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Lung Cancer: NSCLC Treatment: Surgery

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- Primary treatment for early stage (I and II) - Only 25-35% of cases are candidates for - Role in cure, diagnosis, palliation of symptoms

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Lung Cancer: NSCLC Treatment: Radiation

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- Adjuvant treatment and/or palliation - Primary modality for stage I and II if not surgical candidate - Postoperative w/ positive surgical margins - Management of brain mets - Commonly prescribed dosing: 60-70 gray (Gy) in 2-Gy fractions

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Lung Cancer: NSCLC Treatment: Stereotactic ablative radiotherapy (SRT)

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- Highly focused radiation treatment that gives an intense dose of radiation concentrated on a tumor, while limiting the dose to surrounding organs - Used to tx inoperable early stage disease and improves local control

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Lung Cancer: NSCLC Treatment: Radiofrequency ablation (RFA)

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- Whole brain RT and stereotactic radiosurgery for management of brain metastasis and improve quality of life

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Lung Cancer: NSCLC Treatment: Chemo

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- Administered as adjuvant, concurrently w/ RT, or as single modality - Stage III: concurrent chemoradiation is standard - Indicated for individuals w/ good performance status - Cisplatin based doublets

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Lung Cancer: NSCLC Treatment: Cisplatin based doublets

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- SE: N, V, neurotoxicity, kidney damage, fatigue - Standard regimen for treating advanced disease - Cisplatin w/ etoposide, gemcitabine, docetaxel, vinorelibine, paclitaxel - Pemetrexed- superior when histology is nonsquamous - Carboplatin - individuals who cannot tolerate cisplatin (decreased kidney function, hearing loss, neuropathies)

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Lung Cancer: NSCLC Treatment: Targeted therapy (4 drugs)

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- Effective w/ certain genetic mutations - EGRF (epidermal growth factor receptor) mutations sensitive to Tyrosine kinase inhibitor (TKI) - 1. Bevacizumab - increase risk of bleeding - 2. Erlotinim - advanced, recurrent, or metastatic non-squamous NSCLC - 3. Crizotnib - advanced disease and ALK (anaplastic lymphoma kinase) positive - 4. Gerfitinib: approved to treat advanced NSCLC that is epidermal growth factor receptor mutation positive

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Lung Cancer: SCLC - % of cases - % 5 year survival - ? survival w/o treatment

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- 15% of cases - Poor prognosis: 5 yr survival 5-10% - Untreated survival 2-4 months

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Lung Cancer: SCLC treatment

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- Cisplatin and etoposide (doublet chemotherapy regimen) - Prophylactic cranial RT w/ complete response - Carboplatin if contraindications present - Treatment duration: 4-6 cycles

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Multi-hit theory

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-used to explain the blocking of tumor suppressor genes after repeated mutations caused by carcinogenic exposure - "turning-off" of the tumor suppressor genes allows oncogenes to flourish and cancer process to proliferate - hypothesis that cancer is the result of accumulated mutations to a cell's DNA - carcinogenesis depended on both the activation of proto-oncogenes (genes that stimulate cell proliferation) and the deactivation of tumor suppressor genes

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Lung Cancer: Statistics - % of new cancer cases annually - % of cancer deaths in 2013 - % 5 year survival for localized disease

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- 14% of new cancer cases annually - 27% of cancer deaths in 2013 - 52% 5 year survival for localized disease

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Lung Cancer: Cisplatin and Doxetaxel main toxicities

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N/V, neurotoxicity (numbness, tingling, hearing loss, tinnitus, difficulty w/ fine motor movements, difficulty w/ ambulation), immune suppression

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Neoadjuvant therapy

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Administration of a treatment modality before the main treatment

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GI Tract: Esophageal cancer non-modifiable risk factors (9)

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1. Male 2. Tylosis: inherited autosomal dominant condition characterized by palmoplantar keratoderma (a group of disorders characterized by thickening of the skin on the palms of the hands and soles of the feet) 3. Achalasia: a rare disorder in the muscle ring in the lower esophagus fails to relax during swallowing, resulting in decreased peristalsis of food into stomach 4. Esophageal webs 5. HPV 6. Hx of other cancers 7. Hiatal hernia 8. GERD 9. Barrett esophagus

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Tylosis

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-inherited autosomal dominant condition -a group of disorders characterized by thickening of the skin on the palms of the hands and soles of the feet

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Achalasia

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a rare disorder in the muscle ring in the lower esophagus fails to relax during swallowing, resulting in decreased peristalsis of food into stomach

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GI Tract: 5 yr survival rates 1. Esophageal 2. Gastric 3. Pancreatic

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1. Esophageal: 38% 2. Gastric: 27% (second most common cause of cancer related deaths in the world) 3. Pancreatic: 6% (most die w/in 1st yr)

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GI Tract: Gastric cancer non-modifiable risk factors (9)

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1. H. pylori 2. Epstein-Barr Virus 3. Gastric surgery 4. Gastric polyps 5. Gastric ulcers 6. Pernicious anemia 7. Blood group A 8. Family Hx 9. Genetic polymorphisms

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GI Tract: Colorectal cancer non-modifiable risk factors (6)

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1. Age >50 2. Personal or family hx of colon ca or inflammatory bowel disease 3. Hereditary polyposis syndrome 4. presence of adenmatous polyps 5. Familial adenomatous polyposis 6. Lynch syndrome

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GI Tract: Colorectal cancer modifiable risk factors (6)

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1. smoking 2. alcohol use 3. diet high in fat, red meat 4. obesity 5. inadequate intake of fruits and vegetables 6. physical inactivity

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GI Tract: Anal cancer non-modifiable risk factors (3)

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1. hx of cervical, vulvar, or vaginal cancer 2. Immunosuppression 3. Hematologic malignancy

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GI Tract: Hepatocellular cancer non-modifiable risk factors (5)

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1. Hep B (main factor for increased incidence) 2. Hep C (ain factor for increased incidence) 3. Hemochromatosis 4. Alpha-1-antitrypsin deficiency 5. Cirrhosis

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GI Tract: Pancreatic cancer non-modifiable risk factors (4)

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1. Advancing age 2. Male gender 3. African Am. Ethnicity 4. Ashkenazi Jewish heritage

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GI Tract: Esophageal squamous cell carcinoma

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1. arises from squamous cell epithelium 2. more common in developing nations 3. usually in upper 2/3s of esophagus

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GI Tract: Esophageal adenocarcinoma

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1. arises from glandular tissue 2. affects mostly distal esophagus 3. r/t GERD and Barrett esophagus; alcohol and smoking

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GI Tract: Gastric Adenocarcinoma

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1. 95% arise from glandular epithelium in stoma 2. most common gastric cancer, 90% of all malignancies 3. Two types: Intestinal or diffuse a. Intestinal: associated w/ chronic atrophic gastritis, retained glandular structure, little invasiveness, and sharp margin; better prognosis; no family hx b. Diffuse: consists of scattered cell clusters w/ poor differentiation and dangerously deceptive margins; associated w/ genetic factors, blood type, family hx

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GI Tract: Metastatic pattern: Esophageal

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1. Most common: liver and lung 2. via lymphatics and hematogenously 3. Others: pleura, stomach, peritoneum, kidney, adrenal, bone, brain

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GI Tract: Metastatic Pattern: Gastric

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1. direct extension to adjacent organs - liver, diaphragm, pancreas, spleen, and colon 2. hematogenously to liver 3. directly into perineum

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GI Tract: Metastatic Pattern: Colorectal

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1. local extension through penetration of bowel 2. hematogenously to liver and lung

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GI Tract: Metastatic Pattern: Anal

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1. Direct extension into pelvis 2. intra and extra pelvic lymph nodes 3. hematogenously into lung and liver

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GI Tract: Metastatic Pattern: hepatocellular

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1. Rarely metastases due to tumor poor prognosis 2. Metastases late- lung, portal vein, periportal nodes, bone, brain

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GI Tract: Metastatic Pattern: Pancreatic

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1. Usually via lymph nodes 2. Hematogenously into liver and lung

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GI Tract: Treatment: Esophageal cancer

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1. Surgery: a. Tis and Stage I - Endoscopic mucosal resection b. Stages I to III - Esophagectomy 2. Radiation a. Concurrent w/ chemo as neoadjuvant or definitive therapy; Stage IV - palliative 3. Chemo a. W/ radiation as neoadjuvant or definitive b. Primary tx for stage IV

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GI Tract: Treatment: Gastric cancer

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1. Surgery: a. Endoscopic mucosal resection for Tis and T1b b. Subtotal or total gastrectomy T1b-T3 c. en bloc resection of involved structures in T4 tumors 2. Radiation: a. postoperatively w/ concurrent chemo to decrease incidence of local recurrence 3. Chemotherapy: a. Perioperative b. Metastatic disease: palliation, improved survival and QOL 4. Biotherapy: a. Trastuzumab (Herceptin) - HER2+ tumors in metastatic setting w/ chemo

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GI Tract: Treatment: Colorectal

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1. Surgery a. Right sided: right hemicolectomy b. Transverse colon: extended right hemicolectomy c. Left sided: left hemicolectomy d. Sigmoid colon: anterior sigmoid colectomy e. Rectal: local excision or low anterior resection 2. Radiation: neoadjuvant or adjuvant w/ chemo to decrease local recurrence or palliative 3. Chemo: a. Not indicated for stage I b. Neoadjuvant: for unresectable tumors; with concurrent radiation for locally advanced c. Adjuvant: 5FU alone or w/ oxaliplatin (Eloxatin) 4. Metastatic: 5FU w/ oxaliplatin or irinotecan (Camptosar); Irinotecan as single agent; chemo in conjunction w/ biotherapy 5. Biotherapy: advanced or metastatic disease a. Bevacizumab (Avastin) b. Cetuximab (Erbitux)- KRAS mutation c. Panitumumab (Vectibix) - KRAS mutation d. Regorafenib (Stivarga) -used as a single agent only e. Ziv-alferbecept (Zaltrap) - used w/ irinotecan

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GI Tract: Treatment: Anal cancer

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1. Radiation: a. definitive w/ chemoradiation for stages I-III b. palliative for stage IV 2. Chemo: a. Early stage: definitive therapy, concurrent combination chemo (5FU and mitomycin) and radiation b. Metastatic: cisplatin and 5FU

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GI Tract: Treatment: Hepatocellular

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1. Surgery: a. Partial hepatectomy b. Transplantation 2. Embolization a. Chemoembolization b. Bland embolization c. Radioembolization 3. Radiation - alternative to ablation or chemoembolization 4. Systemic chemo- low response rates, no survival benefits 5. Targeted therapy: Sorafenib (Nexavar) - unresectable HCC

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GI Tract: Treatment: Pancreatic cancer

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1. Surgery: a. Pancreatoduodenectomy (Whipple) b. Distal pancreatectomy - left sided resecton c. Stenting - dune for obstructive symptoms 2. Radiation a. Palliative b. concurrently w/ chemo 3. Chemo a. Adjuvant: 5FU, leucovorin, capecitabine b. metastatic or unresectable: 1. Folfirinox (combination of 5FU, leucocorin, irinotecan, and oxaliplatin) 2. Gemcitabine and abraxane 3. Gemcitabine and erlotinib 4. Gemcitabine and cisplatin 4. Targeted Therapy a. Erlotinib in conjunction w/ gemcitabine

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GI Tract: Helicobacter pylori (H. pylori)

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- bacterial infection that occurs in stomach - present in 66% of population - cause peptic ulcers and gastric ca - not associated w/ pancreatic, liver, or colorectal ca

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Rx: Oxaliplatin

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- Chemotherapeutic agent - tx of gastric cancer and GI malignancies - prior to gastric resection to eradicate micrometastases and reduce tumor burden - classified as an alkylating agent. - Alkylating agents are most active in the resting phase of the cell. These drugs are cell-cycle non-specific

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GI Tract: Colon cancer symptoms and tumor location

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- Transverse colon: blood in stools, changes in bowel patterns, symptoms of early bowel obstruction - Descending colon: abd pain, obstructive symptoms, constipation alternating w/ diarrhea - Ascending colon: vague abd pain, weakness, wt loss, changes in stool, anemia - Rectum: rectal fullness, urgency, bleeding, pelvic pain

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Tumor markers: CEA, CA19-9, CA 27-29; a-fetoprotein

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1. CEA: colorectal cancer 2. CA 19-9: pancreatic cancer 3. CA 27-29: breast cancer 4. a-fetoprotein: liver and testicular cancer 5. CA-125: ovarian cancer

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Cervical cancer: Metastatic patterns

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1. Direct extension into parametrium, vagina, lower uterine segment, abdomen, other pelvic structures 2. lymph nodes 3. hematologic to lung, liver, bone

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Cervical cancer: Symptom triad indicating possible recurrent disease

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1. unilateral leg edema 2. sciatic pain 3. urethral obstruction (Testing: abdominal CT, ultrasound, MRI, or PET scan)

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Cervical cancer: high risk individuals (8)

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1. immunosuppression 2. Diethylstilbestrol (DES) exposure in utero 3. chronic corticosteroid tx 4. HIV 5. smoking increases risk 2-5 times 6. average age 45-55 7. Long term oral contraceptive use 8. High parity

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Cervical cancer: Diagnostic procedures (4)

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1. Colposcopy 2. cervical biopsy 3. endocervical curettage 4. Cone biopsy or look electrosurgical excision (LEEP)

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Colposcopy

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- a medical diagnostic procedure to examine an illuminated, magnified view of the cervix and the tissues of the vagina and vulva - cervix swabbed w/ acetic acid solution - no douche, vaginal creams, or intercourse w/in 2 days before - not menstruating

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Cervical cancer: Bethesda System describing Pap results (3)

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1. Negative for intraepithelial lesion or malignancy 2. Epithelial cell abnormalities (squamous and glandular cells) 3. Other malignant neoplasms (melanoma, sarcomas, lymphoma)

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Cervical cancer: Biopsy reports (4)

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1. CIN1: mild dysplasia; low grade 2. CIN2: moderate dysplasia; high grade 3. CIN3: severe dysplasia and carcinoma in situ 4. Squamous cell cancer of cervix

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Cervical cancer: Medical management: Pre-invasive disease

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Biopsy, cauterization, cryotherapy, laser therapy, conization, loop electrosurgical excision procedure (LEEP), hysterectomy

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Cervical cancer: Medical management dependent on (3)

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1. size and location of CIN (cervical intraepithelial neoplasia) 2. Desire to preserve child bearing capacity 3. Physicians skill/preference

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Cervical cancer: Medical management: Invasive disease

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Surgery or radiation or both

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Cervical cancer: Fertility sparing surgery

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a. stage 1A1 and no lymphovascular space invasion (LVSI): cone biopsy w/ negative margins b. Stage 1A1 w/ LVSI or 1A2: cone biopsy w/ negative margins or radical trachelectomy(surgical removal of cervix) and pelvic dissection c. Radical trachelectomy and pelvic node dissection

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Cervical cancer: Non-fertility sparing

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a. Stage 1A1 w/ no LVSI - observation if cone biopsy margins are negative and not surgical candidate - Extrafascial hysterectomy -Extrafascial hysterectomy or modified radical hysterectomy if margins positive b. Stage 1A1 w/ LVSI or 1A2 - modified radical hysterectomy w/ pelvic lymphadenectomy; consider para aortic lymph node sampling c. Stage 1B1 or 2A2 - radical hysterectomy, pelvic lymph node dissection, para aortic lymph node sampling

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Cervical cancer: Radiation tx

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1. External and high dose outpatient or inpatient intracavitary brachytherapy implantation 2. Radiosensitization w/ cisplatin based chemo

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Endometrial cancer: Cause and types

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a. caused believed to be r/t chronic endogenous or exogenous estrogen exposure b. 85-90% adenocarcinoma c. rarer types: clear cell, uterine papillary serous, sarcoma histologies

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Endometrial cancer: risk factors

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a. Increased incidence r/t: increased use of estrogen w/o progestational agents and obesity b. Lynch syndrome up to 60% higher risk c. age: 50-59 d. Menopausal (80% post menopausal) e. Triad: obesity, diabetes, HyperT f. nulliparity, early age of menarche, late menopause g. use of tamoxifen h. endometrial hyperplasia I. breast, ovarian, or colorectal, endocrine related cancer

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Endometrial cancer: metastatic pattern

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a. Inner third to full thickness of endometrium b. Local extension to adjacent structures such as cervix and vagina, intra-abdominal sites and lung c. Femoral, iliac, hypogastric, para aortic, and obturator lymph nodes d. Hematologic: uncommon in type I, more common in serous and sarcoma histologies

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Endometrial cancer: Staging reported as (5)

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a. anatomic stage b. histopathologic grade c. depth of myometrial invasion d. peritoneal cytology e. hormone receptor status

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Endometrial cancer: Treatment: Pre invasive

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a. Hormone tx or simple hysterectomy b. Fertility sparing: hormone therapy w/ interval endometrial sampling (not standard of care)

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Endometrial cancer: Treatment: Invasive

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a. Surgery Staging: TH-BSO w/ peritoneal cytological exam, pelvic and para aortic lymph node dissection b. Surgery for cervical involvement: radical hysterectomy w/ pelvic and para aortic lymph node dissection c. Adjuvant Radiation - Preoperative: extensive lesions involving cervix or high grade -Postoperative: high risk for recurrent, high grade, deep myometrial invasion - techniques: intra cavity brachytherapy or external beam c. both

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Ovarian cancer: Metastatic pattern

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a. Local extension to adjacent organs (bladder and colon) b. Exfoliation of ovarian capsule (transported throughout peritoneum by physiological peritoneal fluid and disseminate throughout intra abdominal cavity) c. Serosal seeding throughout peritoneal cavity including omentum d. lymphatic spread (pelvic and periaortic) e. hematologic spread RARE **aggressive disease

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Ovarian cancer: risk factors

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a. age 45-65; peak 60-64 b. germ cell more common in children/adolescents c. Infertility/Nulliparity d. hx of breast, endometrial or colon ca e. family hx of breast, endometrial, or coon (BRCA 1 or 2 mutation, Lynch syndrome) (Hereditary ovarian ca accounts for 5%)

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Gestational Trophoblastic Neoplasia (GTN)

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a group of rare tumors that involve abnormal growth of cells inside a woman's uterus; does not develop from cells of the uterus like cervical cancer or endometrial (uterine lining) cancer do. Instead, these tumors start in the cells that would normally develop into the placenta during pregnancy

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Gestational Trophoblastic Neoplasia (GTN): Metastatic pattern

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Lung, vagina, liver, brain

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Vulvar cancer: Metastatic pattern

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a. direct extension to adjacent structures b. lymph node metastases: femoral, inguinal, and iliac nodes c. Hematogenous to lung

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Vaginal cancer: Staging

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Stage I: limited to vaginal wall Stage II: subvaginal tissue, not pelvic wall Stage III: pelvic wall Stage IV: beyond pelvis or involves pelvis, bladder, or rectum Stage IVb: distant organs

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Vaginal cancer: Treatment

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a. Preinvasive: localized tx (topical agent, laser vaporization) b. Invasive: surgery, RT, both c. Recurrent: surgery or RT

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Abdominal carcinomatosis

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- a type of secondary cancer that affects the lining of the abdominal cavity - symptoms: abdominal swelling, wt gain, lower leg edema, SOB, loss of appetite, nausea, fluid and electrolyte imbalance, malabsorption, constipation, fatigue

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Testicular cancer: metastatic pattern

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a. direct extension to adjacent structures b. lymphatic spread c. hematologic metastasis to lung, brain, bone, liver

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Testicular cancer: Risk factors

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1. between the age 15-35 2. cryptorchidism (undescended testicle) 3. Klinefelter syndrome (genetic d/o of males born w/ one or more extra X chromosome) *50% seminomas, spread slowly through lymphatics, responsive to RT

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Testicular cancer: Treatment: Surgery

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a. Transinguinal orchiectomy: primary for seminomas and nonseminomas b. Retroperitoneal lymph node dissection c. Resect residual disease and metastatic lesions

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Penile cancer: metastatic patterns

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a. direct extension to adjacent structures b. metastasis to reginal lymph nodes: inguinal and iliac

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Penile cancer: Risk factors

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a. 50-80% r/t HPV b. phimosis (a congenital narrowing of the opening of the foreskin so that it cannot be retracted) c. poor penile hygiene d. chronic inflammation e. tobacco use f. HIV g. lack of circumcision

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Kidney cancer: Major classifications (7)

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1. Clear cell carcinoma (70-80%) 2. Papillary renal cell carcinoma (10%) 3. Chromophobe renal cell carcinoma (5%) 4. Collecting duct (Bellini) carcinoma (;1%) - Subtype: Renal medullary carcinoma (RMC) - occurs in men w/ sickle cell 5. Unclassified renal cell carcinoma 6. Tumors of renal pelvis (;5%, very rare) 7. renal cell cancers **metastasis at dx in 30%; recurrence in 40%

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Renal medullary carcinoma

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- Type of renal cell cancer - Occurs almost exclusively in children and young adults w/ sickle cell - Most younger than 10 - More male than female

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Triad of symptoms for renal cell carcinoma

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1. hematuria 2. pain 3. flank mass

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Kidney cancer: Risk factors

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- Tobacco, obesity, HyperT, unopposed estrogen use, diuretic treatment, Prior RT - occupational exposure to petroleum products, heavy metals, asbestos - dialysis acquired cystic kidney disease - Diet: high fat, high protein, low antioxidants - Genetic: von Hippel-Lindau disease, non-Hodgkin lymphoma, sickle cell disease

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von Hippel-Lindau disease

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a rare genetic disorder characterized by visceral cysts and benign tumors in multiple organ systems that have subsequent potential for malignant change.

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Kidney cancer: common metastatic

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sites Lung, abdominal and mediastinal lymph nodes, liver, bone

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Kidney cancer: Treatment options

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1. Surgery 2. Cryosurgery and radiofrequency ablation 3. Active surveillance 4. Radiation (UNRESPONSIVE to) 5. Chemo (NOT SHOWEN TO IMPROVE SURVIVAL) 6. Immunotherapy (Interleukin-2 and/or interferon-alpha) 7. Targeted therapies **30% have metastatic disease at dx

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Bladder cancer: Major classifications

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1. Urothelial carcinoma (95%) 2. Squamous cell (1-2%) 3. Adenocarcinomas (1%) 4. Small cell (;1%)

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Bladder cancer: Risk factors

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- Tobacco use (most significant; 50-66% in men; 25% in women) - Diet: high fried meats and fats - Diet high in vitamins A, E, and zinc - protective - Occupational exposure to: cyclic chemicals (benzenes and arylamines), chemicals used in dyes, rubbers, textiles, paints, leathers

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Bladder cancer: Common metastatic sites

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Lymph nodes, bones, lung, liver, peritoneum

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Bladder cancer: Medical management

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1. Transurethral resection of tumor (TURBT) 2. Intravesical therapy: chemotherapy and immunotherapy 3. Radical cystectomy w/ urinary diversion (includes removal of prostate/hysterectomy) 4. External beam RT 5. Trimodality therapy: transurethral resection, RT, Chemo

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Combination Chemotherapy: MVAC

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Methothrexate, vinblastine, doxorubicin, cisplatin

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Medical management: Luteinizing hormone-releasing hormones

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- Decrease production of testosterone - fewer side effects then estrogens - give with Flutamide to reduce "flare" (sudden exacerbation of symptoms including cord compression and ureteral obstruction)

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Prostate cancer: Major classifications

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1. adenocarcinomas 95% 2. Sarcomas, mucinous or signet ring tumors, adenoid cystic carcinomas, small cell undifferentiated 5%

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Prostate cancer: Risk factors

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1. Age: 75% 65 years or older 2. African American 3. Dietary factor: High fat diet 4. Occupational exposure: farming, cadmium exposure (welding and battery manufacturing) 5. Genetic: BRCA 1 or 2; 1st degree relative w/ 3 fold risk increase; 1st and 2nd degree, 6 fold

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Prostate cancer: Common metastatic sites

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Lung, liver, adrenal glands, kidneys, bones

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Cancer Staging

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Stage refers to the extent of cancer. • Where the tumor is located in the body • The cell type (such as, adenocarcinoma or squamous cell carcinoma) • The size of the tumor • Whether the cancer has spread to nearby lymph nodes • Whether the cancer has spread to a different part of the body • Tumor grade, which refers to how abnormal the cancer cells look and how likely the tumor is to grow and spread

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Tumor Grade

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the description of a tumor based on how abnormal the tumor cells and the tumor tissue look under a microscope. It is an indicator of how quickly a tumor is likely to grow and spread. If the cells of the tumor and the organization of the tumor's tissue are close to those of normal cells and tissue, the tumor is called "well-differentiated ." These tumors tend to grow and spread at a slower rate than tumors that are "undifferentiated" or "poorly differentiated," which have abnormal-looking cells and may lack normal tissue structures.

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Skin Cancer: Primary causes (2)

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1. UVR (ultra violet radiation) - Two types: UVA and UVB 2. Genetics: Xeroderma pigmentosum, oculocutaneous albinism, basal cell nevus syndrome, familial atypical mole melanoma syndrome

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Skin Cancer: Xeroderma pigmentosum

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an inherited condition characterized by an extreme sensitivity to ultraviolet (UV) rays from sunlight. This condition mostly affects the eyes and areas of skin exposed to the sun.

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Skin Cancer: oculocutaneous albinism

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a group of rare inherited disorders characterized by a reduction or complete lack of melanin pigment in the skin, hair and eyes. These conditions are caused by mutations in specific genes that are necessary for the production of melanin pigment in specialized cells called melanocytes.

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Skin Cancer: familial atypical mole melanoma syndrome

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(FAMMM) syndrome is an autosomal dominant genodermatosis characterized by multiple melanocytic nevi, usually more than 50, and a family history of melanoma

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Skin Cancer: basal cell nevus syndrome

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autosomal dominant pattern; telltale sign of this disorder is the appearance of basal cell carcinoma (skin cancer) after you enter puberty.

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Skin Cancer: Basal cell carcinoma

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1. arises from basal cell layer of epidermis 2. Caused by combination of cumulative and intense UV exposure 3. Most common form of skin cancer 4. rarely metastasizes, may become ulcerated and locally invasive 5. more common in older adults

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Skin Cancer: Squamous cell carcinoma

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1. arises from squamous cells layer of epidermis 2. caused by cumulative UV exposure over a life time 3. 2nd most common 4. local recurrences may lead to metastasis and death 5. slow growing 6. presents as new or enlarging lesion that may bleed, weep, be tender or painful 7. indurated, rounded, superficial or discrete w/ hyperkeratotic (thicken) scale 8. numbness, tingling, or muscle weakness indicate perineural invasion 9. high risk w/ HIV and immunodeficiency

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Skin Cancer: Melanoma

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1. arises from malignant proliferation of melanocytes 2. primary cause: intense, occasional UV exposure 3. most common cancer in adults 25-29; second in ages 15-29 4. lymph node biopsy if >1mm or <1mm and ulceration or mitosis

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Skin Cancer: melanocytes

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1. pigment producing cells 2. originate from neural crest 2. migrate to skin, meninges, mucous membranes, upper esophagus, and eyes

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Skin Cancer: Melanoma prognostic features (2)

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1. Breslow depth: depth of invasion in millimeters 2. Ulceration of primary lesion defined as absence of intact epidermal layer

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Skin Cancer: Melanoma metastatic pattern

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Regional lymph nodes, distant skin, subcutis, lung, liver, and brain

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Skin Cancer: Nodular Basal cell carcinoma

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1. 50-80% of all basal cell carcinomas 2. most likely on head or neck 3. round, pink, pearly, flesh-colored papule w/ central depression 4. Telangiectasia (dilation of small blood vessels) seen w/in lesion 5. may be crusted, ulcerated, or bleeding

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Skin Cancer: Superficial Basal cell carcinoma

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1. 15% of all basal cell carcinomas 2. found on trunk 3. bright red to pink patch; scaly 4. slowly progressive

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Skin Cancer: Micronodular basal cell carcinoma

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1. aggressive 2. yellow-white when stretched 3. firm to touch

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Skin Cancer: Superficial spreading melanoma

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1. 60-70% frequency 2. Any site; lower extremities in females; back both 3. common in fair skinned 4. begins as brown/black macule w/ color variations 5. asymmetric, poorly circumscribed 6. notching and scalloping common 7. 25% associated w/ preexisting nevus

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Skin Cancer: Nodular melanoma

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1. 15-30% frequency 2. primarily sun exposed head, neck, trunk 3. male>females 4. presents as deeply invasive lesion 5. dark brown-black to blue modules, may be pink to red 6. highest risk of recurrence and metastasis because of ability to invade dermis w/ no horizontal growth

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Skin Cancer: Endogenous risk factors

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Phototype, skin/eye color, number of nevi, individual/family hx

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Skin Cancer: Exogenous risk factors

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Type and degree of cumulative sun exposure, hx of sunburns, sun protection behavior

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Skin cancer: Melanoma recognition (ABCDEs)

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A: Asymmetry (one half unlike other) B: Border (irregular, scalloped, uneven) C: Color (varied; more than one present w/in lesion) D: Diameter (>6mm) E: Enlarging or evolving

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Head and Neck: metastatic pattern

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1. locally aggressive 2. spread to regional lymph nodes 3. distant sites: lung, liver, bone 43% nodal involvement; 10% distant mets at dx Most Stage III or IV at dx

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Head and Neck: Histology classification

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1. 90% Squamous cell 2. 10% adenocarcinoma (salivary glands), melanoma, sarcoma, or lymphoma

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Head and Neck: Risk factors: Oral cavity Salivary glands Paranasal/Nasal Nasopharynx Oropharynx Hypopharynx Larynx

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Oral cavity: HPV Salivary glands: Radiation Paranasal sinuses and Nasal: wood or nickel dust Nasopharynx: Asian (Chinese), Epstein-Barr, wood dust Oropharynx: Poor hygiene, mechanical irritation, high alcohol mouthwash Hypopharynx: Plummer-Vinson syndrome Larynx: asbestos **Tobacco increase risk 25 fold **Excessive alcohol 9 fold

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Plummer-Vinson syndrome

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Rare disorder, leads to difficulty swallowing do to webs of tissue across upper esophagus

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Trismus

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-spasm of the jaw muscles, causing mouth to remain tightly closed -possible SE of RT to head/neck -jaw exercises reduce stiffness, increase opening

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Neurologic system: Brain tumor histologies (6)

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1. gliomas (astrocytoma, oligodendroglions, mixed) 2. Ependymomas 3. Primitive neuroectoderma cells (PNETs) (Medulloblastomas, Ependymoblastomas, Pinealbblastms 4. Primary CNS Lymphoma 5. Meningioas 6. Neuromas

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Cranial Nerves

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1. Olfactory 2. Optic 3. Oculomotor 4. Trochlear 5. Trigeminal 6. Abducens 7. Facial 8. Auditory (Vestibulocochlear) 9. Glossopharyngeal 10. Vagus 11. Spinal (Accessory) 12. Hypoglossal

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Neurologic: Metastatic patterns of primary CNS tumors

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1. Rare to metastasize outside of CNS 2. May invade dura and adjacent structures 3. Drop metastases to spine 4. Seeding in CSF

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Common sites that metastasize to brain (5)

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Lung: Most frequent (>90% will develop w/in 1 year) Breast: not as common as lung; develop in 2-3 years Melanoma Renal Colorectal

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Common sites that metastasize to spine (4)

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Breast, Lung, Prostate, MM

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SE of radiation tx to CNS: Acute

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**During and immediately following 1. Inflammation 2. radiation induced demyelination 3. Global: HA, neurocognitive changes, seizures, somnolence 4. Focal: specific defects based on tumor location

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SE of radiation tx to CNS: Subacute

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** 4 weeks to 6 months following 1. Causes: Radiation demyelination, Inflammation, altered capillary permeability radionecrosis 2. Toxicities: somnolence, exacerbation of tumor symptoms 3. MRI: tumor progression vs pseudoprogression

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SE of radiation tx to CNS: Late

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** 6 months to 1 year following Radiation necrosis, diffuse white matter changes, neurocognitive effects, cerebrovascular events, optic nerve toxicities, endocrine toxicities, secondary malignancies (meningiomas, gliomas, nerve sheath)

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First line glioma treatment

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-Temozolomide (Temodar): oral, second generation alkylating agent which can permeate blood brain barrier -Combined w/ radiation therapy in high grade gliomas

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First line treatment for CNS Lymphoma

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High dose methotrexate based regimen

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Movement across blood brain barrier dependent on:

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particle size, lipid solubility, chemical dissociations, protein binding potential

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Known intrinsic risk factors for CNS tumors:

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Gender: Male- glioma; women- meningioma Age: Children and elderly Race: Whites, Northern European **African Americans have highest risk

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4 lobes of brain and what they control

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Occipital: sight Parietal: sensory input like pain and temp Frontal: personality, mood, intellect Temporal: Hearing, memory, receptive speech

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Rx: Temodar

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- oral, second generation alkylating agent - can permeate blood brain barrier - w/ radiation to treat high grade gliomas

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Known Situational risk factors for CNS Tumors

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1. Hx of viral infection: Epstein-Barr (CNS lymphoma) 2. Immunocompromised 3. Hx of head trauma associated w/ meningiomas 4. Personal cancer hx

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Known extrinsic risk factors for CNS tumors

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1. Ionizing radiation 2. Children w/ leukemia treated prior to age 3. Panorex x-ray prior to age 10

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Diagnostic imaging of neurologic system: CT w/ and w/o contrast uses

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1. w/o contrast: in emergency r/o stroke vs lesion, detect hemorrhage and calcification 2. w/ contrast: surgical and RT planning, visualize malignant tumors

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Diagnostic imaging of neurologic system: MRI w/ and w/o contrast uses

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1. w/o gadolinium: evaluate edema, nonenhancing tumors, RT induced leukoencephalopathy, acute blood products, visualize high grade tumors Pre-op: identify edema, locate mass Post-op: (24hrs) residual tumor volume, new baseline Follow-up q3-4 months 2. w/: visualizing brain and spine lesions, disease surveillance

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Leukemia

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1. malignant d/o of blood cells and lymphatic tissues, most commonly involving WBC's 2. Leukemic cells infiltrate: spleen, liver, CNS, lymph nodes 3. classified according to cell type: myeloid or lymphoid 4. classified as acute or chronic 5. 90% diagnosed in adults (AML and CLL most common)

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Acute leukemia's

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1. excessive proliferation of immature blast cells 2. Two classifications: AML (most common) and ALL (most common in children and teens)

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Chronic leukemia's

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1. excessive proliferation of functionally incompetent cells 2. Onset gradual, dx incidental 3. Two types: CML and CLL (most common)

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Leukemia's risk factors

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1. previous tx w/ antineoplastic agents (alkylating and topoisomerase inhibitors); 2. Tx w/ medications: chloramphenicol and phenylbutazone 3. Accidental or work related exposure to chemicals 4. Human T-cell leukemia virus type 1 5. inherited genetic d/o 6. smoking (AML and CML) 7. Previous exposure to radiation

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Leukemia's S;S

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1. Chronic- asymptomatic 2. r/t bone marrow failure: recurrent infections, neutropenia, thrombocytopenia, anemia 3. r/t organ and lymphatic infiltration: lymphadenopathy, bone pain, early satiety, fullness/abdominal discomfort (splenomegaly and hepatomegaly) 4. Seizure w/ CNS involvement

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Tumor lysis panel

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LDH, uric acid, potassium, calcium, phosphorus

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Leukemia epidemiology

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1. 90% in adults 2. CLL and AML most common 3. ALL most common in children and teens 4. rates increasing

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Diagnostic criteria: CLL

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1. ;5x10 to 9th power/L (5000microliters) B-lymphocytes in peripheral blood for at least 3 months 2. may present at repeated infections and/or enlarged lymph nodes

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Diagnostic criteria: CML

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1. Presence of Philadelphia chromosome; translocation between chromosomes 9 and 22 (BCR-ABL1 fusion gene) 2. FISH (florescence in situ hybridization) determine presence of BRC/ABL1 chromosome

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Diagnostic criteria: ALL

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1. 20% lymphoblasts in bone marrow 2. 25% of adults will also have Positive Philadelphia chromosome 3. may present w/ enlarged lymph nodes, bone pain, fever, night sweats, fatigue

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Diagnostic criteria AML

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1. 20% myeloid blasts in bone marrow 2. may present w/ early satiety, easy bruising, gingival/nose bleeds, overwhelming systemic infection

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Autoimmune cytopenias

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autoimmune hemolytic anemia immune thrombocytopenia PRCA (pure red cell aplasia)

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chronic lymphocytic anemia

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- characterized by continual accumulation of B cells in bone marrow and peripheral bloodstream - small portion of B cells can produce antibodies leading to autoimmune d/o - autoimmune hemolytic anemia, immune thrombocytopenia, pure red cell aplasia (PRCA) - 5-10 % of CLL patients develop

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Leukemia's staging system: AML CML ALL CLL

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AML - no staging system CML - no staging; three phases: chronic, accelerated, and blastic ALL - no staging; risk stratification: Adult high (Philadelphia chromosome +) or low risk (Philadelphia -) CLL - Rai staging system (low, intermediate or high)

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Common S&S of CLL

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1. early satiety and wt loss 2. Splenomegaly 3. fatigue, malaise 4. Lymphadenopathy (axilla, clavicular, supraclavicular, groin)

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Rai staging system

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CLL staging system 1. Low: lymphocytosis (lymphoid cells >30%), no other symptoms 2. Intermediate: lymphocytosis; lymphadenopathy in any site, splenomegaly, or hepatomegaly 3. High: lymphocytosis; anemia (hgb <11) or thrombocytopenia (plt <100) w/ or w/o lymphadenopathy, splenomegaly, or hepatomegaly

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ALL categorized as low or high risk: Low risk High risk

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Low risk: B-cell, children 1-9 yrs, WBC 50,000 at dx

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Virchow triad

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associated w/ pathophysiology of venous thromboembolism (VTE) 1. Stasis: bed rest and/or extrinsic compression of vessels by tumor 2. Vascular injury: direct invasion by tumor, prolonged central catheters, endothelial damage secondary to chemo 3. hypercoagulability: release of tumor associated procoagulants and cytokines, impaired endothelial cell defense mechanisms, and/or reduction of naturally occurring inhibitors

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Salvage therapy

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loosely defined as treatment prescribed for patients after standard treatment has failed

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Leukemia: Induction therapy

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- goal to attain complete response and repopulate bone marrow w/ normal cells (less that 5% blasts and normal blood counts) - Cytarabine plus an anthracycline (Idarubicin or daunorubicin)

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Leukemia: Consolidation therapy

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given after induction has attained complete remission to reduce leukemic cell population and achieve long-term disease free survival

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Hodgkin Lymphoma: Risk factors

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- malignancy of lymphoid system - teens and adults age 15-35 and >55 - cause unknown - risk factors: age, Epstein-Barr or HIV, family hx, primary immunodeficincies, prior solid organ or bone marrow transplant, prior tx w/ chemo

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Hodgkin lymphoma: clinical presentation

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- enlarged lymph nodes, spleen or other immune tissue w/ or w/o systemic symptoms - B symptoms (systemic symptoms): fever, wt loss, fatigue, night sweats lymph nodes most often involved: cervical, supraclavicular, mediastinal, axillary, inguinal - presence of Reed-Sternberg cells

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Staging Hodgkin lymphoma

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- Ann Arbor Staging system - based on extent of disease and presence of systemic (B) symptoms - four prognostic groups *Stage 1: single lymph node involvement *Stage 2: two or more lymph nodes, same side of diaphragm *Stage 3: involvement on both sides of diaphragm *Stage 4: Disseminated involvement ***If fever, night sweats, or wt loss (>10%), then B designation added to stage

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Non-Hodgkin lymphoma: Risk factors

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median age at dx: 66 Cause unknown Immunodieficiency, infection w/ EBV (Burkitt lymphoma), infection w/ HTLV-1 (T cell lymphoma), HIV, H. pylori infection (MALT lymphoma), environmental/occupational exposure

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Non-Hodgkin lymphoma: clinical presentation

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- painless lymphadenopathy - pruritus, fatigue, abdominal pain (enlarged spleen or liver), bone pain - most often presents as disseminated disease in extranodal sites (bone marrow, liver) - most advanced at presentation (Stage 3-4)

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Multiple myeloma: Risk factors

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- exposure to radiation, metals (nickel), family hx, African American, >60 years

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Multiple myeloma: Clinical presentation

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- bone pain from lytic lesions (back and chest) - increased levels of heavy-chain M proteins - Increased levels of light chain protein in urine - Bence Jones proteins (M proteins) - Myeloma related organ dysfunction (CRAB): - C: elevated calcium >10.5 ng/L - R: Renal insufficiency, serum creatinine >2 mg/dl - A: anemia, hgb <10 g/dl - B: Bone lytic lesions - beta 2 macroglobulin levels reflect tumor mass

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Multiple Myeloma: Staging

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International staging system (ISS): Stage I-III based on beta-2-microglobulin and albumin in blood

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Common cancers of the bone: (3)

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Osteosarcoma, Chondrosarcoma, Ewing sarcoma

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Osteosarcoma Tissue of Origin: Common locations: Age: Metastasizes: Clinical symptoms:

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Tissue of Origin: Osteoid Common locations: Knees, upper legs, upper arms Age: 10-25 years Metastasizes: Lung Clinical symptoms: Pain, swilling, pathologic fracture; visible, palpable, firm, non tender, warm mass; limited ROM * elevated alk phos

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Chondrosarcoma Tissue of Origin: Common locations: Age: Metastasizes: Clinical symptoms:

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Tissue of Origin: Cartilage Common locations: Pelvis, upper legs, shoulders Age: 50-60 years Metastasizes: slow growing, may metastasizes locally Clinical symptoms: Dull, aching pain; firm, swollen area; high grade tumor may appear soft, viscous

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Ewing sarcoma Tissue of Origin: Common locations: Age: Metastasizes: Clinical symptoms:

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Tissue of Origin: immature nerve tissue, usually in bone marrow Common locations: Pelvis, upper legs, ribs, arms Age: 10-20 years Metastasizes: highly malignant (20-30% w/ at time of dx); lung, lymph nodes, other bones Clinical symptoms: progressive pain, lump, flue like symptoms, fever, fatigue, anemia * spreads to adjacent tissue via many round cells w/ indistinct borders * 40-70 become disease free survivors * appear onion like on radiographs

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Occurrence sites and rates of primary bone cancer: (6)

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Lower extremity 41% Pelvis 26% Chest wall 16% Upper extremity 9% Spine 6% Skull 2%

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Skip metastases

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-Often seen in patients w/ osteosarcoma - smaller areas of the same tumor occurring in the same bone but anatomically separated from primary lesion

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Incidence of soft tissue sarcomas and corresponding sites: (3)

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extremities 50% trunk and retroperitoneum 40% head and neck 10%

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Myoma

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benign tumor that grows in the muscle layer of the uterus, usually of women age 40-60

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Rhabdomyosarcoma

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- occur in infants - 19 yrs - arise from striated muscle - usually present in head, neck, genitourinary, arms, legs, neck

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sarcomas

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- can occur anywhere in body, most often in lower extremities and trunk - incidence higher in men - frequently metastasize to lung - present w/ dull aching pain that increases at night

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AIDS defining malignancies (4)

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1. non-Hodgkin lymphoma - B cell lymphoma most common 2. Burkitt lymphoma 3. Kaposi sarcoma - incidence decreasing r/t advent of combination antiretroviral tx 4. Cervical cancer

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HIV related Kaposi Sarcoma

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- cancer that develops from the cells that line lymph or blood vessels - causes lesions to grow in the skin, lymph nodes, internal organs, and mucous membranes lining the mouth, nose, and throat - often affects people with immune deficiencies - Purple, red, or brown skin blotches are a common sign

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HIV quick facts (7)

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- HIV-1 is more virulent than HIV-2 - average time from HIV to AIDS is 2-3 yrs - average life expectancy 11-14 yrs - disease progression affected by presence of many viruses, inadequate nutrition, general poor health, smoking - Increased risk w/ uncircumcised males r/t dendritic cells on foreskin - Heterosexual women comprise 15% of HIV dx/yr - African americans and Lationos excessively affected

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HIV and malignancies associated w/ viral infection facts

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- more accelerated conversion to malignancy - comprises 58% of all cancers in HIV - less likely to be r/t viral load or CD4 count compared to AIDS-defining malignancies - present w/ aggressive disease and high risk of metastasis compared w/ non-HIV - more common in whites, males - occur at younger age compared w/ non-HIV

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Factors associated w/ shorter survival in patients w/ HIV related lymphoma (5)

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- CD4 count <100 - stage 3-4 disease - older than 35 yrs - hx of IVDA - elevated lactate dehydrogenase

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Body fluids for which universal precautions DO apply (9)

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- blood - CSF - semen - vaginal secretions - synovial fluid - amniotic fluid - pericardial fluid - pleural fluid - peritoneal fluid

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Histopathology of HIV related lymphoma (4)

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- majority are intermediate or high grade B cell type - Small call lymphomas typically found in bone marrow an meninges - Large cell more likely found in GI tract - lesions are painful and may be mistaken for KS

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Treatment options for primary central nervous system lymphoma (3)

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Rituximab High dose methotrexate (>3g/m2) High dose cytarabine (>2g/m2)

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Prognosis of pt w/ Kaposi sarcoma and HIV dependent on:

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- location of presenting lesions - survival shorter w/ GI lesions, B symptoms, and/or prior opportunistic infections - survival increased w/ cART

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CDC HIV infection staging system

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Stage 1: Lab conformation of HIV and CD4 >500 Stage 2: Lab conformation of HIV and CD4 between 200-249 Stage 3: Lab conformation of HIV and CD4 <200 Unknown: Lab conformation of HIV and unknown CD4 count

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Walter Reed Staging system for HIV

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- Stage 1: positive HIV antibody, CD4 >400 - Stage 2: positive HIV antibody, chronic lymphadenopathy present, CD4 >400 - Stage 3: positive HIV antibody, chronic lymphadenopathy present, CD4 <400 - Stage 4: positive HIV antibody, chronic lymphadenopathy present, CD4 <400, partial positive tb skin test - Stage 5: positive HIV antibody, chronic lymphadenopathy present, CD4 <400, complete positive tb skin test, oral thrush - Stage 6: positive HIV antibody, chronic lymphadenopathy present, CD4 <400, partial or complete positive tb skin test, oral thrush, opportunistic infections

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Potential complication of high dose cyclophosphamide (Cytoxan)

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1. hemorrhagic cystitis - administration of Mesna (a uroprotectant) - Frequent voiding - accurate I&O 2. hyponatremia r/t SIADH

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Potential side effects of: Melphalan Thiotepa Etoposide

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1. Melphalan: alteration in oral mucous memebranes - cryotherapy 2. Thiotepa: excreted via integumentary system - skin problems - frequent showers 3. Etoposide: Cardiovascular SE - monitor BP and HR; Decreased LOC r/t alcohol content

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Veno-occlusive disease (Hepatic sinusoidal obstruction syndrome)

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- early complication of HSCT, occurring between day 3-21 - characterized by hepatomegaly, right upper quadrant pain, jaundice, and ascites - hepatic venous outflow obstruction to occlusion of the terminal hepatic venules and hepatic sinusoids - preexisting liver disease increases the risk of developing

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Idiopathic pulmonary interstitial pneumonitis

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- chest RT and/or bleomycin tx increases likelihood - occurs most frequently in clients >30yrs - interventions: activity, turning, coughing, deep breathing - IV or aerosolized abx - expansion of the interstitial compartment (ie, that portion of the lung parenchyma sandwiched between the epithelial and endothelial basement membranes) with an infiltrate of inflammatory cells - inflammatory infiltrate is sometimes accompanied by fibrosis, either in the form of abnormal collagen deposition or proliferation of fibroblasts capable of collagen synthesis

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Ionizing radiation

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- used to treat cancer - RT interact w/ atoms and molecules of tumor cells to produce harmful biological effects to molecules of cell and cell environment - two forms: Electromagnetic & particulate

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Electromagnetic ionizing radiation

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- radiation in form of energy waves - includes photons - x-rays, gamma rays

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Particulate ionizing radiation

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- radiation in form of subatomic particles - includes electrons, protons, neutrons, alpha particles, and beta particles

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Biologic effects of ionizing radiation

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- Cellular target: DNA - Direct effect on cell: single and double strand breaks, formation of cross-links - Indirect effect: ionization of water creating free radicals that damage DNA

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Biologic response to radiation affected by:

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- level of DNA damage - oxygen effect (well-oxygenated tumor show greater response) - sensitivity of cell to radiation

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Time in which biologic changes appear and nature/severity of effects of radiation depend on:

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- amount of radiation absorbed - fractionation - rate at which it is administered

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Oncology Review – Flashcards

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