M1: Onco Concepts & Cancers in Canada

how does cell become tumour

Normal/somatic cells will divide and differentiate but may undergo a gene mutation ⇒ ∴ cause uncontrolled proliferation and lack of differentiation bc of…

1. 1) Activation of oncogenes via DNA mutation – causes activation of a lot of uncontrolled proliferation 

2. 2) Deactivation of tumor suppressor genes  – ∴ unable to stop uncontrolled proliferation (ū able to) 

gene mutations come from…

Exposure to carcinogens, inherited, random

proliferation

rapid and sudden increase in the number, amount, or spread

benign vs malignant tumours

Benign tumors: encapsulated cell with relative organization, well differentiated, normal mitotic rate, able to expand and compress to nearby tissues but doesn't invade, doesn't metastasize 

Malignant tumors: not well encapsulated/unorganized, can be well differentiated/undifferentiated, normal-increased mitotic rate, will infiltrative/invade, metastasize, can cause death 

what does prefix of a tumour tell u?

provides info about cell, organize, or tissue of origin 

what does suffix of tumour tell you

provides info about the type of tumour

carcinoma-

tumour in epithelial tissues

sarcoma-

comes from connective tissues

adenocarinoma-

comes form columnar/glandular epithelium tissues

-oma

benign tumour

-carcinoma

malignant tumour

-sarcoma

malignant tumour

leukemia

blood forming tissues

lymphoma

• exception to the -oma suffix rule (should be benign but is always malignant) tumour in lymphmatic system

astrocytoma

affects CNS cancer

glioblastoma

• exception to the -oma suffix rule (should be benign but is always malignant) tumour in CNS

medulloblastoma

• exception to the -oma suffix rule (should be benign but is always malignant) tumour in CNS

epidemiology

study of disease incidences

• refers to… age, demographics, populations, patterns of occurrence, death rates 

incidence

# of newly diagnosed cases during a specific period of time 

prevalence

# of TOTAL cases of disorder (eg. cancer) in a defined population at a particular point in time 

mortality rate

# of deaths occurring in a specific population during a year

lifetime risk

probability of developing or dying of cancer

etiology

study of CAUSE of disease – incl. risk factors from syndromes/genetic

risk factors

trait, condition, or behavior that increases your overall chance of developing cancer

carcinogens

known cancer-causing agents 

• Can be behavioral, environmental, biological (eg. hormones), genetics factors

things we should know about anatomy and physiology in terms of cancer

• organ anatomy

• blood supply

• lymphatic drainage

• normal physiological function

natural history and route of spread

what the progression of hte tumour would be if there was no treatment/intervention

• looking for growth rate, route of spread, tendency to metastize early/late

types of routes of spread of cancer

1. local invasion

2. lymphatics

3. blood

local invasion

AKA direct invasion — growth of tumour within the organ it originates from. During early stages = within the organ, but during advanced stages = may break through the membrane to nearby tissues 

exophytic growth vs endophytic growth

1. Exophytic growth: tumour grows outwards 

2. Endophytic growth: tumours grows inwards – may invade into layers/penetrates structures

fixed invasion

tumor has grown (invaded) into surrounding, tissues, anchoring it in place so that it cannot be easily moved

regional spread

cancer cells trapped in lymphatic fluid/node and travel to the next node

hematogenous spread

100% metastasis and go anywhere in body

seeding

cells breaking off of tumour and form another tumour there OR during surgery, will transfer cancer cell residue 

clinical presenation

indications of disease, illness, injury, or when something isn’t ‘right’  

sign vs symptoms

Sign: objective observations (eg. rash) 

Symptom: subjective feelings/notices but not easily observable (eg. nausea) 

localized

Localized: occurs in small area/one spot

non-specific

Non-specific: no particular reason of why something is happening (eg. weight loss, fatigue, pain) 

procedures taken when cancer is suspected (diagnositc methods)

1. Medical history – eg. allergies, past medical history, prior treatment/surgery, family with similar disease, lifestyle

2. Physical exam – irregular masses, visual cues, changes in color, edema, pain, 

   1. Auscultation – listen to sounds of the heart, lungs, abs, bowel 

   2. Take vital signs – bp, temperature, heartrate 

3. Laboratory studies – bloodwork studies (cells and quantity) vs blood chemistry (components of blood), urine/fecal study, immunological studies, genetic 

4. Medical imaging – eg. ultrasound, xray, CT, MRI, PET 

5. Biopsy – taking sample of tumour to test histologically (confirm diagnosis)  

6. ⇒ if maligant… need to determine stage/grade of disease

tumour markers

can show if cancer is present, or monitor pt response to treatment

differential diagnosis vs clinical diagnosis vs pathological diagnosis

Differential diagnosis: possible ideas of what the pt can be suffering from based on signs and symptoms  

Clinical diagnosis: doctor’s diagnosis based on medical history, physical exam, lab study, and medical imaging

Pathological diagnosis: after clinical diagnosis where you need to examine histology of cell (ū via biopsy) 

incisional biospy

removes only part of the tumour and is limited in use

punch biopsy

• common, requires anesthesia, obtains mucosal deep layer sample

Excisional biopsy

has the largest margins (takes the entire lesion and margins)

Fine needle aspiration

takes a few cells out from tumour, minimally invasive, 

• Deep masses = via endoscopy + FNA (may be ultrasound guided) 

• Ū common for breast, thyroid, lymph

endoscope

light and camera at the end of fibre optic cable, placed inside body to visualize area + US to aid in biopsy of tumour

⤷ may use anesthesia

laryngoscopy

vocal chords

bronchoscopy

trachea, main, and segmental bronchi

mediastinoscopy

• mediastinal masses/nodes; operative (procedure-invasive/leaves suprasternal scar) 

colonoscopy

colorectal track, can remove polyps

Proctoscopy/sigmoidoscopy

anal canal, rectum +/- sigmoid 

cystoscopy

urethra, bladder, ureters

colposcopy

vagina, cervix

laparoscopy

structures in the abdominal cavity

dermatoscopy

asses melanoma

screening vs diagnostic vs staging test

Screening test: detects disease before it manifests clinically (early signs) 

Diagnostic tests: done to arrive at a diagnosis 

Staging tests: done to assign disease a stage once confirmed it’s malignant cancer

prognosis

expected course or outcome of a disease – pt’s chance of recovery 

⤷ prognostic factors can influence the outcome of a disease (tumour, treatment, pt factors) 

purpose of prognosis

Helps determine appropriate treatment, help make decisions abt their lives/course of treatment, analyze outcome of the treatment, analyze data from clinical trials

5-year survival

pt has gone 5 years since the last of their cancer treatment… what is the likihood of survival given each stage:

• Stage I – 80-95%

• Stage II – 60-75%

• Stage III – 25-45%

• Stage IV – 0-15%

radical intent vs palliative intent

Radical intent: purpose of cancer treatment is to CURE (eliminate all tumour, achieve long-term control) 

Palliative intent: purpose of cancer treatment is to minimize/treat symptoms (improve quality of life, reduce pain etc

neoadjuvant role vs adjuvant role

Neoadjuvant role: first step of treatment, done to prior to the primary treatment given (eg. chemo is radiosensitizer to RT, shrinking the tumour before surgery…) 

Adjuvant role: extra cancer treatment given after a primary treatment (eg. chemo used to treat residual disease) 

surgery

• Surgery – local control; removal of the primary tumour 

  • Roles ⇒ primary modality, neo-adjuvant OR adjuvant role 

  • Radical or palliative intent 

  • Factors to consider ⇒ size, extent and location of tumour, operative risks

chemotherapy

• Chemotherapy – systemic control, uses cytotoxic drugs/hormones to kill cancer cells (typically when metasistized) 

  • Roles ⇒ primary modality for systemic cancer (eg. leukemia), neoadjuvant (radiosensitizer to RT) , adjuvant role (treat residual disease) 

  • Radical or palliative intent 

  • Sanctuary sites (places that's hard to target) = CNS, testes

radiation therapy

• Radiation therapy – local control and improvements 

  • Roles ⇒ primary modality, neo-adjuvant (shrink tumour), or adjuvant (kill cancer or unsure surgical margins) 

  • Radical or palliative intent 

  • Benefits ⇒ preservation of function, better cosmetic results, ability to reach inoperable areas in body

immunotherpay

• Immunotherapy – using your body’s own disease-fighting system to destroy cancer (Car-T cell therapy)

  • can be specific (using antigens to trigger immune response) or non-specific (stimulate immune system in a general way) 

  • Roles ⇒ adjuvant role 

  • Radical or palliative intent

targeted therapy

Targeted therapy – drugs or other substances that interact with specific genes/proteins in cancer cell to either block instructions to proliferate/induce death (eg. herceptin (trastuzumab) for breast cancer pt w HER+ve)

Factors to consider when thinking about cancer treatment: 

1. Comorbidities (other medical conditions) 

2. Pt performance status 

3. Pt preference (they always have the final say – may vary from the optimal choice) 

clinical trials

research-based evidence about specific effectiveness of new treatment, looking for ways of treating-preventing-diagnosing medical conditions (incl. Drugs, technology) 

retrospective study vs prospective study

Retrospective study: looking at previous data and analyzing it 

Prospective: conducting a study to ‘discover new’ research

phase I, II, III of clinical trials

Phase I: beginning of study – looking at ethics, effectiveness, viability 

Phase II: adding more people — looking for more significance and results 

Phase III: look at results and compare to the standard/conventional treatment 

preventation

reducing cause of cancer will reduce # of cancer mortalities 

• Done by… 

  • Avoid carcinogens (tobacco, sun exposure etc) 

  • Pursuing healthy lifestyle (exercise, diet, sex life) 

  • Participate in screening/early detection 

  • ⇒ aided by public awareness, education, public health policies, (chemical) barriers (eg. sunscreen), lifestyle choices

sensitivity vs specificity

Sensitivity: ability to test for people who HAVE the disease (true-positive rate) 

• A 100% sensitive test will always detect disease when its present 

• A 60% sensitive test will only detect the disease 60% of the time when its positive (but 40% false negatives) 

Specificity: ability for a test to correctly identity people who do not have the disease (true-negative rate) (saying u have cancer, but you dont) 

• A 100% specific test will never indicate disease when its not present 

• A 70% specific test will indicate there IS a disease 30% of the time when it is NOT present (30% false positive) 

stages of the cell cycle

• 1) G0 – cells are fully performing function

• 2) G1 – first growth phase: rapid growth and active metabolism, synthesizing RNA and proteins to carry out cell functions to prep for DNA replication 

  • Time period may vary 

• 3) S-phase –  synthesis phase: DNA replication occurs 

  • ∴ Chromosomes are duplicated so daughter cells receive identical genetic material 

• 4) G2 – second growth phase: more cell growth and more proteins and enzymes 

  • Ū Shorter period 

• 5) M – mitotic phase: prophase, metaphase, anaphase, telophase ⇒ 1 parent cell divides into 2 identical daughter cells 

what cell cycle stage are cells the most sensitive to radiation

** cells are most sensitive to radiation in late G2/M phase bc they are actively prepping for cell division (S-phase is least sensitive bc it can just resynthesize damage) 

theory of cancer initiation

• Cancer initiation occurs when normal cell growth/differentiation is disrupted because of mutations 

• Somatic cells have genes that promote or suppress growth. If mutation, genes with uncontrollable proliferation (if targeted promoting genes) or will not allow for apoptosis (will not die if targeted suppress growth) 

  • Proto-oncogenes (normal growth-promoting genes) may convert into oncogenes ⇒ stimulating excessive cell proliferation 

  • Antioncogenes (tumour suppressing gene) may lose their ability to control cell growth ⇒ uncontrolled division

proto-oncogenes

• proto-oncogene: normal growth-promoting gene

oncogene

• oncogene: mutated gene that has the potential to cause normal cells to become cancerous by driving uncontrolled cell growth and division

antioncogene

• antioncogene: tumour suppressing gene — normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die

example of epidemiological data vs etiological data

Epidemiologic data example: 

• There is a higher incidence rate of prostate cancer in African-American males 

• Studies trends in cancer occurrence (eg. recent decreases of lung cancer in men, decline of stomach cancer, increase in malignant melanoma in the US) 

Etiological data example: 

• Cigarette smoking is a risk factor for cancer and started putting explicit images of lung damage on printed on the front of each box 

• Sun exposure is a risk factor for skin cancer – led to development of sunscreen

multicentric tumour

when 2+ tumours grow in same organ/tissue system (ū eg. breast)

advanced local spread

tumour spreading to nearby tissues/organs

metastasis process

1. Local invasion – break through boundaries of og tissue 

2. Intravasation – cells squeeze through the walls of nearby blood/lymphatic vessels 

3. Circulation – cells travel through body transport channels 

4. Extravasation – cells exit vessels at a distant site 

5. Colonization – cells adapt to new organ and grow new tumour

2 main channels of metastasis

circulatory system (hematogenous spread) and lymphatic system (regional spread)

Do the majority of cancer cells that gain access to routes of spread, successfully metastasize?

No. When cancer is in the circulatory system/lymphatic vessels, will face immune response, physical stress, lack of growth signals → ū die before they can form secondary tumours 

common metastatic sites for lung cancer

Lung cancer ⇒ liver, adrenal glands, bones, brain 

common metastatic sites for breast cancer

Breast cancer ⇒ lungs, bone, brain  

common metastiatc site for prostate cancer

Prostate cancer ⇒ bones, liver, lungs

common metastatic site for anal cancer

Anal cancer ⇒ liver, lungs

characterisitics of optimal screening

• Identify cancer in its earliest stages (before symptoms appear) 

• Must be sensitive (ability of a test to give a true-positive result) and specific (ability of the test to obtain a true-negative result)

• Affordable

false-positive vs false-negative findings

False- pos finding: test shows cancer is present when there actaully ISN’T 

• Causes unnecessary anxiety, additional testing, unnecessary treatment 

False-neg finding: appears that there is no cancer present when there ACTUALLY IS cancer 

• Consequences = delya in diangosis and treatment, disease may progress

syndrome

A syndrome is a collection of signs and symptoms that occur together and characterize a disease or condition

5 components of a medical history

• Chief complaint

• History of present illness

• Past medical history 

• Family histoyr 

• Social history (eg. habits of smoking, alcohol, obesity) 

components of a physical history

• Inspection – visually 

• Palpation – feeling around 

• Percussion – tapping on the body check the size, shape, and density of internal organs through the sounds produced

• Auscultation – listen to internal sounds of heart, lungs, abs, bowel 

• Vital signs 

objective vs subjective diagnosis

Objective diagnosis: based on observable or measurable findings (CT, MRI, PET, biopsy results, lab results).

Subjective diagnosis: based on pt symptoms (pain, hoarseness, bloating, discomfort), or medial history

homeostasis vs necrosis vs apoptosis

Homeostasis: self-regulating process of maintaining a balanced, internal environment (eg. pH)

Necrosis:  dead tissue (may be bc of lack of blood, oxygen, nutrient) 

Apoptosis: programed cell death

inflammation

immune system's protective response to injury, infection, or harmful irritants, working to eliminate threats and heal damaged tissue

inflammation process

1. injury/infection occurs ⇒ tissue damaged 

2. Chemical mediators released 

3. Blood vessels dilate (↑blood to site = red/hot) 

4. BV more permeable (fluid + WBC move into tissue and cause swelling) 

5. WBC attack cause 

6. Tissue repair starts

common agents that cause tissue damage

Physical, chemical, infectious, hypoxia, immune reaction, nutritional imbalances

anaplastic vs pleomorphic

Anaplastic: loss of differentiation – cells appear more primitive and less like normal cells 

Pleomorphic: variation in cell size and shape – characteristics of malignat tumors  

Does every mutation result in cancer?

No. cancer ū only happens if it affect growth-regulating genes and need multiple for cell to be malignant