therapeutic options in cancer Flashcards
therapeutic options can be …
preventative or treatments
prevention
environment/behaviour diet screening genetics medication/vaccination
treatment
surgery
radiotherapy
systemic therapy
immunotherapy
diet
inconsistent evidence and lots of confounding factors
CRC: probably linked with red meat consumption
breast cancer: probably a link with saturated fat intake
physical activity decreases risk
also a benefit for reducing CVD
environment
○ Smoking in public places
○ Minimal alcohol pricing
○ Water and air quality: electric cars, renewable energy
○ Vaccination: HPV/Hep B
○ Opportunities via school: physical activity, school meals
○ Income and housing policies
For medical profession: importance of public health specialists and GPs
screening
high quality research evidence available
Age of screening varies with cancers
cervical cancer screening
regular smear tests (should become rarer due to introduction of HPV vaccine in young girls(13y/o))
CRC cancer screening
faecal occult blood the most commonly used test
16% reduction in CRC mortality
breast cancer screening
mammography
problems with screening
sometimes gives false reassurance to patients, investigations also come with risk which needs to be considered
Population that take part in screening tend to be healthier and wealthier (i.e. people who don’t turn up tend to be more at risk and this can lead to health inequalities)
genetics
- More targeted than screening
- High quality research evidence available
○ CRC and FAP (familial adenomatous polyposis coli)
○ Breast cancer and BRCA1/2:
CRC and FAP (familial adenomatous polyposis coli)
§ autosomal dominant
§ screen families for APC mutations
§ regular colonoscopy
§ offer panprotocolectomy when adenomas found - remove colon and rectum to prevent cancer as one of the polyps is almost guaranteed to become cancerous
breast cancer and BRCA1/2
§ These genes increase risk of breast cancer
§ also important in therapeutic area
Chemo-prevention
- More controversial - give people medication to prevent them getting cancer
limited effectiveness - Primary: oesophageal cancer
- Primary: breast cancer
- Secondary: previous H&N or lung cancers
chemo - prevention: oesophageal cancer
○ High rates in parts of China and Iran
○ Thought to be related to diet (particularly in Iran)
○ Supplement diet with anti-oxidants - didn’t make a lot of difference
chemo-prevention: breast cancer
○ Known at risk women
○ Prophylactic tamoxifen - tamoxifen has side effects which need to be considered
chemo-prevention: previous H&N or lung cancers
○ Give anti-oxidant supplements
○ No benefit
treatment can be …
local, regional or systemic
local or regional treatment
○ Surgery
○ Radiotherapy
○ Ablation (freezing, radio-frequency etc)
Isolated limb perfusion
systemic treatment
○ Hormonal therapy ○ Chemotherapy ○ Biological therapy ○ Immunotherapy ○ CAR T-cell therapy Whole body irradiation (BMT)
define cancer staging
Staging is a way of describing the size of a cancer and how far it has grown
cancer staging process
- Where is cancer
- Examination
- Uses of radiology/imaging
○ CT, MRI, USS, PET etc - What kind of cancer
- Pathology/cytology
○ Classification, risk factors etc
○ Genomics now plays a role and will increase
○ Immune/stomal environment will also have a role - this can effect the variety of treatment options that are possible
surgery needs anatomical …
clearance
must go round the ‘holy plane’ to reduce chances of recurrence
radiotherapy needs anatomical …
coverage
radiotherapy benefits (over surgery)
- Can treat inoperable lesions
- Can make surgery become possible - or can avoid the option of surgery completely
Can maintain function and appearance
- Can make surgery become possible - or can avoid the option of surgery completely
5 R’s of radiotherapy
radiosensitivity
repair and repopulation
re-oxygenation
reassortment
radiosensitivity
some tumours are more sensitive than others meaning certain treatment options can be excluded (i.e. avoiding treating something with something that may not even work)
repair and repopulation
e.g. H&N cancer, treat 3x per day, no breaks can improve survival
re-oxygenation
if cells are low in oxygen they are much more resistant to treatment
reassortment
at different stages of the cell cycle, cells are more sensitive to different agents
systemic treatment
Beneficial for widespread disease, can result in widespread toxicity, now mixture of chemotherapy and now targeted agents
Targeted agents in systemic treatment
potential to be very specific
Tamoxifen and ER +ve breast cancer
EGFR mutations and TKI agents
Indications for the use of systemic therapies
- Curative
- Adjuvant - where someone has had a successful operation but they have a statistical risk of recurrence
- Neoadjuvant - common with rectal cancer, give someone the treatment upfront with the view of getting them to surgery
- Palliative - improve and maintain QOL
chemotherapy and therapeutic index
trials find dose regimen to balance anti-cancer activity versus toxicity
targeted therapies
- Specific based on molecular science
- Imatinib: blocks a tyrosine kinase, very useful in CML and GISTS
- EGFR inhibitors - EGFR mutation in lung cancer, don’t give chemotherapy w/ EGFR mutation as it has little effect, more beneficial to give targeted therapy
In lung cancer need to have a specific mutation
immune therapies are either
specific or non-specific
non-specific immune therapies
○ Innate: macrophages, NK cells
Programmed cell death pathway (PD1): uses immune system to attack foreign cancer cells (cancer cells hide from the immune system), agents strip away mask from cancer cells so they are identified as FOREIGN
specific immune therapies
○ Monoclonal antibodies: rituximab and B cell NHL: +/- radioactivity; trastuzumab and response in HER2 +ve breast and gastric cancer
§ Also used in non-cancerous conditions e.g. AI, arthritis
Chimeric antigen receptor (CAR) T cells: artificial T cell receptors, using retroviral vectors to give a specific cell killing function directed against cancer cells
mechanisms of checkpoint blockade
- PD1 and PDL1 antagonists
- Now in clinical use (melanoma and lung cancer)
- Success depends on:
○ Mutation burden of cancer
○ Immunogenicity of neoantigens
Most people have minimal side effects
monoclonal antibodies
- Not confined to cancer - can be used in the treatment of other conditions
- Humanised so they can be used in the human body - generally very well tolerated and allergic reactions are rare
- Cancer:
○ CRC and cetuximab
○ Breast and trastuzumab
NHL and rituximab
chimeric antigen receptor T cell therapy
- Used at the moment in haematological cancers
Opportunity to be used in other cancers - need to find stable cancer antigen as it is very specific
