Lecture 1 - Cancer Def., Biology, Screening & Treatments Flashcards
Cancer in Australia: what are the 5 mot common cancers?
Prostate Colorectal (bowel) Breast Melanoma Lung
These account for more than 60% of all cancers.
What is the breast cancer incident rate?
Prostate cancer incidence rate?
Australia has the highest incidence rate (3rd globally)
Australia has the HIGHEST incidence rate world wide
What are the 3 main Cancers more common in younger individuals (<20 y.o.)?
- Brain cancer
- Leukaemia/lymphoma
- Other neoplasms
What are the 4 main Cancers more common in older individuals (>20 y.o.)?
- Lung
- Colorectal
- Breast
- Prostate
Australian Cancer Statistics:
Increased incidence rates?
Decreased mortality rates?
Incidence rate = Aus has the largest increase in cancer indented over the past decade (>20%)
Could be due to better ability to detect and diagnose.
Mortality rate= decreasing mortality rate, due to effective treatments, and on-going management of patients. (Includes the use of exercise and allied health).
What is Cancer?
It defines a group of diseases.
Some of the body’s cells become abnormal and divide without control as a result of changes (mutations) in the generic information of a cell.
If these abnormal cells grow into a lump (mass), it forms what is known as a tumour.
Tumours can be benign or malignant.
Definition of Normal Cell Division:
Normal cell division= 2 daughter cells being produced, cell growth and old cell death.
Apoptosis= self destruction of a cell through programmed cell death (normal cell death)
Initiation of a tumour:
A tumour is initiated when mutation of a cells DNA occurs, affecting the normal growth and division process.
Cell death DOES NOT occur which results in an increased number of dividing cells.
This process leads to a tumour.
Process of Mutation: 3 damaging agents.
Changes in cell DNA (genes) may be caused by mistakes during cell division or exposure to damaging agents in the environment.
- PHYSICAL = Exposure to ultraviolet and ionising radiation
- CHEMICAL= Exposure to asbestos or tobacco
- BIOLOGICAL= Infection (viral, bacteria, parasite)
What is the PROGRESSION of a tumour?
For the tumour to grow bigger, it must grow its own blood vessels. This is known as ANGIOGENESIS
As the tumour grows it starts to invade neighbouring tissues (Invasion)
Sometimes the cells move away from the primary cancer site, via the blood and lymph, and invade other parts of the body. When the cells reach a new site, it grows to form another tumour, this is called METASTASIS.
What are the two types of tumours?
- Benign= non-cancerous tumour. Cells do not spread to other parts of the body.
- Malignant= cancerous tumour. Cells are able to spread to other parts of the body.
Define Metastasis & name characteristics of it:
Cancer cells that have spread from the original growth site to one or more parts of the body, also known as SECONDARY SITES.
It's the development of secondary malignant tumours Originating from primary tumour Located anatomically distant All cancers have the potential to spread Occurs when cells detach from primary tumour Enter circulation or lymphatic Adhere to new tissue - proliferate Lungs most common site for secondaries
Cancer Biology: How are cancers named?
Each cancer is named after the location of its origin
Metastic cancer is a “secondary version” of a “primary cancer” [Prostate cancer which has spread to nodes, organs, or bone is ‘metastic prostate cancer’ or ‘secondary prostate carcinoma’]
Characteristics of a Benign Tumour?
Slow growing Can be quite large Well organised and differentiated Less destructive Can damage adjacent tissues and cause NECROSIS Rarely cause death
Characteristics of a Malignant Tumour?
Cancer cells form malignant neoplasm Highly unorganised Diverse abnormalities Increased invasiveness - metastasis Decreased drug sensitivity Programmed for proliferation Invade normal tissue Intrinsic ability to kill host tissue
Tumour Biology: define the 2 types of solid tumours?
- Carcinoma= originates in skin or epithelial cells of organs [e.g breast, prostate]
- Sarcoma = originates in connective or supporting tissues [e.g. Bone, cartilage, and muscle]
Tumour Biology: define the 3 Haematological (blood) tumours:
- Lymphoma = cancer of the lymph nodes and lymphatic system [e.g. Non-Hodgkin’s lymphoma, Hodgkin Lymphoma]
- Leukaemia = cancer affecting blood, originates in bone marrow. [e.g. Lymphoblastic leukaemia, Myeloid Leukaemia]
- Myeloma - cancer of plasma cells (mature lymphocytes). [e.g. Multiple myeloma, smouldering myeloma.]
Define a Carcinoma:
Solid tumour
Develop in epithelial cells [tissue linings]
Mostly in organs that secrete substances [e.g. Lung, breast, pancreas, kidney, stomach]
85-90% of all cancers are carcinomas
Define Melonamas:
‘Skin cancer’
Cancerous growths of melanocytes
Most common in skin but also back of eye, mouth, vagina, anus.
Define Sarcomas:
Solid tumours
Originates in connective tissue - bone, muscle, cartilage, fat.
Rarest form of cancer accounting for less than 2%
Define Leukaemia:
Cancer of blood forming organs
Result of abnormal white blood cells
2% of all cancers
Invades vital organs such as liver, lungs, heart, brain - organ dysfunction.
Define Lymphomas:
Malignant cancers of lymphocytes
Originate in lymphatic system
5% of all cancer cases
Hodgkin’ - progress in order from lymph node group to next
Non-Hodgkin’ - widespread within lymph system.
Define a Cancer Patient:
A person who has been diagnosed/receiving treatment.
Define a Cancer Survivor:
A person who, is living with cancer, from the time of diagnosis, through all disease stages, until death.
4 types of screening and diagnosis procedures across cancer types:
Specific examples:
- Tissue biopsy [common/necessary]
- Imaging [MRI, CT, PET, Bone]
- Blood pathology [tumoral markers]
- Physical exams
- faecal occult blood test [bowel]
- mammogram [breast]
- colonoscopy [colon/bowel]
- pap smear [cervical]
- prostate specific Antigen Test [Prostate Cancer]
Define Tissue Biospy:
Required to diagnose presence of cancer
Involves collections of cells/tissues/blood
Most common forms of biopsies are:
- endoscopic
- bone marrow
- excision or incision
- fine needle aspiration
- punch biopsy
- shave biopsy
- skin biopsy
Define Imaging:
Confirms presence and distribution of tumours:
- aids in identifying tissues involved/ tumour load
- helps with staging and grading of primary tumours
- guides cancer treatments and treatment response
- monitor for cancer recurrence/progression
Several imaging techniques used:
CT, PET, SPECT, MRI, Bone Scan, X-ray/ultrasound.
Define Pathology Tests:
Blood collection can also be taken to identify cancers = useful to detect cancers early [before visibility on imaging]
Effective for haematological [non-solid] tumours.
Searches for circulating tumour cells and/or antibodies
Used due to patient safety/speed of analysis
Used due to early detection capacity
Physical Exams
- effective to routine examination of solid tumours in regions accessible
- can be [relatively] non-invasive and inexpensive, and inform need for further tests.
-important for several cancers such as:
Prostate cancer [digital rectal examination]
Colon cancer [colonoscopy]
Testicular cancer [digital examination]
Breast cancer [mammogram]
Skin cancer, and/or [skin checks]
Cervical cancer [pap smear]
Often requires regular check-ups to enable early detection.
Define Staging and Grading of Cancers:
Staging is a way of classifying the extent of a person’s cancer.
Useful for determining treatment and estimating prognosis.
The TNM system is commonly used and considers:
- Tumour Size
- Nodal Involvement
- Metastases
Some cancers are also graded based on biology:
- can be slow moving or aggressive
- can be hormone responsive or naive
- can be chemotherapy or naive
Staging - TNM
Stage
Size
Lymph nodes
Metastasis
Stage I, <2cm, none, none
Stage II, 2-5cm, no or yes on same side, none
Stage III, >5cm yes on same side, none
Stage IV, doesn’t matter, doesn’t matter, yes
Define Remission:
Term used to describe the temporary diminution of disease
- rarely are solid cancers permanently cured [even despite surgery]
- even in remission, micro-metastasis may exist/ lay dormant/ undetected
- haematological cancers, while curable, often shorten life span due to treatment aggressiveness
Define Recurrence:
Used to describe the return of cancer after treatment and remission
- local recurrence= returns to same location
- regional recurrence= returns to nearby location [usually lymph nodes of prior cancer]
- distant recurrence= returns in another part of the body.
Recurrence risk depends on several factors= type of cancer, type of treatments used, time since treatment.
At times no signs or symptoms may be present.
Recurrence detects through routine tests: physical exams, pathology tests, imaging scans.
Cancer treatment is categorised into 3 broad categories:
- Local treatments [surgery, radiotherapy].
- Systemic treatments [hormone therapy, chemotherapy, immunotherapy].
- Targeted treatments [molecular targets, cellular alterations].
Reasons for Surgery:
- local treatment [removal of tumoral tissue]
- may be completed in few hours or over months [e.g. mastectomy]
-Surgery for cancer can be for numerous reasons: Preventative Diagnostic Staging/grading “Curative” De-bulking Palliative Supportive Reconstructive
Acute and Chronic Side effects of Surgery:
Acute:
- pain [most commmon]
- infection
- limited ROM
- Fatigue
- Bleeding [internally/externally]
Chronic:
- pain
- loss of flexibility
- nerve damage
- blood clots
- slow recovery of body functions [bowel activity]
Describe Radiation Therapy:
Commonly referred to as radiotherapy - considered a local/ targeted therapy
High energy rays/ particles to to kill tumour cells or damage to prevent multiplication
Used for primary cancer sites “curatively” and to delay cancer progression
Also used palliatively in advanced cancer patients to mange bone metastases.
External Radiation:
- several to 30min appointments
- 1 treatment , or up to 8 weeks of treatments
Internal Radiation:
- radioactive material is sealed and inserted into body
- implant may remain for several days, or permanently.
Acute and Chronic Effects of Radiation therapy:
Acute effects:
-pain, fatigue, skin irritation, pulmonary, loss of appetite, hair loss, diarrhoea
Chronic Efffects:
-cardiac or lung scarring, loss of flexibility, fractures, fertility problems, sexuality problems.
Exposure to radiation also increases risk of other cancers.
Describe Chemotherapy:
A systemic treatment involving cytotoxicity [poison administration]
Involves the use of drugs to kill or slow growth of cancer cells
Chemotherapy administered through the blood stream
Several types of chemotherapy drugs can be used independent or in combination
What are the 4 ways of administering Chemotherapy:
- intravenously: cannula, central line, peripheral inserted central catheter, port.
- oral, tablets.
- injection into muscle, skin, organ or tumour.
- applied as cream onto skin.
What are the different uses of Chemotherapy:
Can be used intensively [i.e. leukemia]
Can be used indefinitely [i.e. hormone naive cancers]
Patients can be naive to chemotherapy [some types of prostate cancer]
Chemo is used to:
- cure [in many haematological cancers]
- slow tumour growth [primary/secondary tumours]
- palliative [prolong survival, particular bone lesions]
- secondary tumours/ metastases
Description of Chemo treatments:
Duration of chemo depends on cancer type/stage, medicine used, severity of side effects, and treatment success.
Chemo admin, due to cytotoxicity, does shorten life span.
- often a reason for markedly reduced adult lifespan for childhood survivors of cancer.
- decision to use therefore considered approach based on factors above.
Generally given in cycles, or periods of drug administration, followed by rest/recovery.
Treatment may last minutes/hours/days; be weekly/bi-weekly/monthly; or cycled.
Potency [effectiveness] of chemotherapy may be enhanced through exercise.
Acute and Chronic side effects of Chemotherapy:
Acute= fatigue, nausea, anaemia, nerve damage, muscle pain, weight gain, cognitive changes
Chronic= cardiomyopathy, lung scarring, nerve damage, fatigue, Bone loss, leukaemia, hearing loss, premature menopause.
Side effect - Cognitive Impairment:
‘Chemo brain’
- post chemotherapy cognitive impairment
- could be related to may aspects of treatment
- often reported as “chemo fog”.
Risk factors include higher doses of treatments hormone changes or hormone treatments, fatigue, depression, age, psychological distress, genetic predisposition.
Characterised by:
- difficulty thinking, remembering, concentrating, word recall is impaired.
- affects 16-75% of cancer patients.
Side effect - Peripheral Neuropathy:
Often called CIPN [chemotherapy induced peripheral neuropathy]
Impaired sensation in the extremities as a result of cancer treatments may pose specific risks when exercising.
Symptoms are pain, burning, tingling [pins & needles], loss of feeling, difficulty picking up or holding things, balance problems, stumbling, muscle weakness, decreased reflexes.
Can be a short term of ongoing side effect.
Describe Hormone Therapy:
It’s a systemic treatment which targets the endocrine system
Alters the body’s ability to produce natural hormone’s which “feed” some cancers.
Hormone therapy works by:
- blocking cancer cells from being able to receive hormone [receptors].
- blocking production of hormones from certain glands within the body
- surgical removal of glands that produce hormones.
HT may continue for several months to years, and in some cases, can be indefinite systemic therapy [in the case of prostate cancer].
Aim of hormone therapy:
Slowing growth and spread of tumours Improve chances of cure Neoadjuvant [pre-primary treatment] Adjuvant [post-primary treatment] Alleviate symptoms
Tumours are adaptive, and can become resistant to long-term use= thus new second-line therapies are being created in several types of dependent cancers.
Hormone Therapy = Breast cancers.
Breast cancer can be targeted by:
-removal of ovaries [to reduce oestrogen levels]
-medication = tamoxifen [blocks effect of oestrogen on growth of malignant cells]
=aromatase inhibitors [prevents oestrogen production]
= fulvestrant [damages oestrogen receptors]
Hormone Therapy - Prostate Cancer
Removal of testicles [reduce testosterone levels] - orchiectomy
Androgen Deprivation Therapy [injection or orally]:
-inhibitors production of hormones and blocks actions of hormones.
Due to hormone resistance from long-term ADT, new drugs have been created.
Novel anti-androgens are designs to block receptors and secretions of testosterone from other sources.
PC is initially hormone sensitive, though becomes naive over time. Second line antiandrogens now used to prolong blockade.
Acute and Chronic Side Effects of Hormone Therapy:
Acute effects= weight gain, decline in lean body mass,decline in strength, decline in libido.
Chronic effects = osteoporosis, poor quality of life, increased risk of co-morbid conditions [CVD, Diabetes, metabolic syndrome], early onset menopause, infertility.
Breast cancer side effects of Hormone Therapy:
Hot flashes Nausea/vomiting Irregular menstrual periods Fatigue Headaches Early onset menopause Infertility Vaginal dryness/irritation
Prostate cancer side effects of Hormone Therapy:
Hot flashes Impotence Nausea/vomiting Fatigue Balance issues Male breast enlargement Loss of libido Bone loss
Describe immunotherapy:
Also known as ‘Biological Therapy’ - systemically delivered
Aim is to boost the bodies natural ability to fight the cancer
Uses or harvest substances made by the body or in a laboratory
Immunotherapy: 5 broad categories
Therapeutic vaccines
On Olympic virus therapies
Checkpoint inhibitors. [powerful treatment in melanoma cancer, and emerging/developing
Adoptive cell therapies. In Breast, lung and Prostate cancer].
Adjuvant immunotherapies
Often tastes time to develop over months
Can be potent in killing cancer systemically, but also possibly temporary
Doesn’t work for everyone
Aims of Immunotherapy:
- To act as curative therapy
- act as adjuvant therapy
- stop/ slow growth/ invasion of cancer.
- boost immune system to be more effective.
Describe Gene Therapy:
Modification of immune response [e.g. increase tumour recognition.]
Modification of cancer tumours with genes with anti-tumour effects [e.g. tumour suppressor genes]
Introduce genes into hematopoetic stem cells to decrease toxicity from chemo
Modification to promote formation of new blood vessels
Describe Vaccine Therapy
Preventative - reduce cancerous activity of bacteria or virus.
Therapeutic- activate the immune system to destroy cancer cells.
Acute and Chronic side effects of Immunotherapy:
Acute= weight gain or loss, fatigue, flu-like symptoms, nerve damage, skin rash/swelling/ low BP
Chronic= nerve damage, myopathy.
Describe Skeletal pharmacology:
Patients often experience bone fragility due to a range of factors:
- type of cancer
- stage of cancer
- type of treatment
Clinicians often prescribe bone strep thing agents, however, these also. Induce a level of fragility when chronically taken.
Can be oral, subcutaneous injections or applied intravenously.
Acute and Chronic effects of skeletal pharmacology:
Acute effects= fever, headache, fatigue, weakness, nausea, diarrhoea
Chronic effects = joint pain, hypocalcaemia, bowel movement changes, osteonecrosis [jaw], excessive sclerosis.
Explain Cancer related fatigue:
Cancer patients experience fatigue far more disruptive to QOL than any other disease.
Over whelming, whole body tiredness not related to activity or exertion.
Prevalence - 72% to 95% of patients receiving therapy
45% after one week chemo, further 33% after two weeks.
CRF is characterised as: [5]
- Severe and distressing
- Persistent
- Not consistently alleviated by sleep or rest.
- Not in proportion to recent activity
- Interferes with daily activities and social functioning.
Symptoms of CRF can be:
- Be present at diagnosis as symptom of cancer
- Develop during cancer treatment
- Develop following treatment as a late effect.
What Factors contribute to CRF?
Change in metabolism Hormonal changes Chronic stress response Anxiety & depression Anemia Altered sleep patterns Treatment side effects= pain, nause, dyspnea
Perceptions of Fatigue:
- 78% of patients experienced fatigue significant enough to effect daily living
- 61% said more significant than pain
- patients believe treatments cause fatigue but doctors state cancer causes fatigue
- only 35% of doctors offer treatments for fatigue
- rest strategy exacerbates fatigue- deconditioning
Physiological Mechanisms causing Fatigue:
Diarrhoea, vomiting, loss of appetite - loss of nutrients, fluid and electrolytes
Neurotoxicity
Reduced cardiovascular function, cardiac output
Decreased lung capacity and diffusion
Reduced RBC - lower oxygen
Reduced activity - lower fitness
Psychological Factors
Depression
Cognitive problems
Stress, worry, anxiety
Attentional fatigue due to extra work of managing treatment, appointment, family, work, etc.
Lymphoedema
Swelling due to blockage of lymph system Due to scarring after node removal Discomfort, pain, loss of function Exercise important Monitoring limb size
Depression and Anxiety
20-50% of cancer patients
Related to lack of physical health, helplessness, pain, body image
Manifested in decreased communication, insomnia, lethargy, fatigue
Mood swings, forgetfulness, cognitive, problems.
