5. Clinical lectures Flashcards
What are the principles of cancer treatment?
- aim to kill cancer cells, but spare normal cells
What are the recent developments of cancer therapy aiming to maximise therapeutic window?
- refine chemotherapy schedules
- novel targeted agents
- better supportive medications
- immunotherapy
- tailoring of treatment to individuals
- response prediction
- radiotherapy improvements
Describe 3 different Chemotherapy treatment settings
- Adjuvant
- following surgery or radiotherapy, to reduce risk of recurrence
- no way of assessing response
- continue to planned number of cycles, tolerance permitting
Metastatic
- Palliative, to control spread of disease
- measure size changes of metastatic lesions
- improvement in symptoms control/QoL
Neoadjuvant
- To shrink tumours before surgery or radiotherapy, improving chance of cute
- allows clinical, radiological and pathological response assessment and change to alternative therapy in non-responders
Describe Staging of Primary Tumour (T) in Breast cancer
Tis
- Carcinoma in situ
T1
- Tumour 2cm or smaller in greatest diameter
T2
- Tumour >2cm but not greater than 5cm
T3
- Tumour >5cm
T4
- Extension to skin or chest wall
Describe different staging of Regional Lymph Nodes (N)
N0
- No regional lymph node metastasis
N1
- Metastasis in 1-3 axillary lymph node(s)
N2
- Metastasis in 4-9 axillary lymph nodes or rediologically involved internal mammary nodes
N3
- Metastasis in 10 or more axxilary nodes or ipsilateral infraclavicular lymph nodes
Describe different staging of Metastases (M)
Mx
- Not evalulated
M0
- No distant metastases
M1
- Distant metastases
What do you look for on a pathology report of tumour?
breast cancer
- Tumour type
- Associated DCIS/LCIS
- Size
- Grade (1-3)
- Margins
- Lymphovascular invasion
- Nodes
- ER/PgR/HER2 receptor status
Describe Cell surface receptors
- In both normal and cancerous cells, cellular receptors are responsible for translating signals from outside the cell into signals within the cell
- These signals have numerous effects such as growth, proliferation and cell survival
- Receptor activation and cellular signalling are tightly regulated in normal cells
- When signalling pathways are inappropriately activated, growth and spread of cancer cells may result
Describe Cell surface receptors in breast cancer
- Oestrogen receptor (ER)
- Progesterone receptor (PR)
- HER2 receptor
: overexpressed in apprx 20% of breast cacner
: associated with more aggresive cancer/poorer prognosis
: more likely to be ER negative (oestrogen supresses HER2 expression)
What is Endocrine therapy? (breast cancer)
- ER positive tumours susceptible to endocrine therapy
: Tamoxifen
: Aromatase inhibitors (AI) - Less side effects and more convenient than chemotherapy
- Similar response rates to single agent chemotherapy
- Lack of cross-resistance so some merit in changing hormone therapy on progression
What are the examples of Anti HER2 directed therapy drugs? (breast cancer)
Trastuzumab
Pertuzumab
Kadcyla
Describe Metastatic disease (breast cancer)
Incurable
- aim is to control and prevent symptoms
Significant gains in progression-free survival (PFS) and overall survival (OS)
Many patients sequence through 5 or 6 lines or therapy over a number of years
Similar drugs to adjuvant setting
- chemotherapy
- endocrine therapy
- anti HER2 therapy
New agents
- Cdk4/6 inhibitors
- mTOR inhibitors
How is Prostate cancer diagnosed?
- usually through raised PSA blood
- may or may not have symptoms
: bladder frequency
: nocturia
: terminal dribbling/poor stream - Digital rectal examination
- MRI scan
- Transcretal biopsy
Describe Prostate cancer pathology
- PSA level
- Number of biopsy cores involved
- Percentage of tissue involved
- Extracapsular extension/seminal vesicle involvement
- Lymph node spread
Gleason grade
- two added score of 1-5
- subjective
- minimum for cancer is 3+3 =6
What are Radical treatment options (localised disease) for prostate cancer?
Surgery
- open
- Laparoscopic
- Robot-assisted
Radiotherapy - external beam radiotherapy \: Conformal \: IMRT \: IGRT - LDR brachytherapy - HDR brachytherapy
Activev surveillance
Watchful waiting
Describe metastatic Prostate cancer
- most common spread is to bones
- backbone of treatment is testosterone suppression and blockade
: LHRHa
: anti-androgens
: new endocrine therapies = abiraterone, enzalutamide - Chemotherapy
: Docetaxel
: Cabazitaxel - Radium 223
What is the cause of Lung cancer?
Smoking
- cause in 90% of cases
Risk related to extend of smoking
Stop smoking
- immediately reduces risk
Main benefit in those who stop by aged 30
Other risk factors
- environmental, passive smoking, asbestos
- fibrotic lung disease
- family history
What are the two main groups of lung cancer?
Small cell lung cancer (SCLC) 15%
- usually caused by smoking
- aggressive, often mstastatic at presentation
- treated with chemotherapy +/- radiotherapy
- high response rates but relapse quickly
Non-small cell lung cancer (NSCLC) 85% - Three main types \: squamous cell carcinoma \: adenocarcinoma \: large cell carcinoma - Molecular profiling important \: EGFR, ALK, ROS-1, PDL-1
Describe SCLC (Small cell lung cancer)
- Limited stage
- when possible to give curative intent radiotherapy
- best results combining chemo and RT at the same time
- No role for surgery
- Cisplatin/Carboplatin + Etoposide - Extensive stage
- most patients present with metastatic disease
- high response rates to chemo (carboplatin + etoposide)
- often relapses within months
High risk of brain metastases
- benefit of prophylactic cranial irradiation (PCI)
- risk reduction of brain mets from 40% to 15%
- doubles 1 year survival
Prognosis
- extensive stage 8-13 months
- limited stage ~2 years
What are symptoms and signs of lung cancer?
Symptoms - Haemoptysis (coughing blood) - Persistent (>3 weeks) \: cough \: chest/shoulder pain \: dyspnoea (breathlessness) \: weight loss \: hoarseness (laryngeal nerve palsy)
Signs
- neck lymphadenopathy (swollen lymph nodes)
- clubbing on toes and fingers (reduced oxygen)
- stridor (high pitched breath sound)
- pleural effusion (water on lungs)
- pancoast syndrome
- metastatic (bone pain or fractures, brain)
- paraneoplastic (hypercalcaemia, hyponatraemia)
Describe Diagnostic test for lung cancer
Bronchoscopy (central)
CT guided lung biopsy (peripheral)
Endobronchial ultrasound (EBUS)
US guided biopsy of neck nodes
Surgical biopsy
Describe Diagnostic test: imaging regarding
- CXR
- CT
- PET-CT
CXR
- raises suspicion of cancer
CT
- for initial staging (distribution of disease)
PET-CT
- when curative treatment is being considered
- more sensitive for showing metastatic disease and lymph node involvement
Describe Adjuvant chemotherapy in lung cancer
Adjuvant
- given after surgery
Indication
- tumour size >4cm
- and/or Node involvement
4~5% improvement in overall survival at 5 yrs
4 cycles of cisplatin and vinorelbine
start within 12 weeks of surgery
Describe Radiotherapy in lung cancer
Principles
- to deliver a tumorcidal dose of radiation
- relative sparing of healthy tissues
- radiation travels in straight line (collateral damage)
- divide total dose into fractions
- usually one fraction/day
- allows recovery of healthy tissues
What is Stereotactic Ablative Body Radiotherapy (SABR)?
Very high dose radiotherapy in few fractions
Indications
- peripheral lung cancer (<5cm) without nodal involvement
- patients not fit (medically inoperable) or decline surgery
Outcomes
- very good local control
- minimal toxicities
What is Conventional radiotherapy?
High dose radiotherapy over many fractions
Indications
- inoperable non-metastatic disease
- invasion or more extensive nodal (N2) involvement
Treatment limiting side effects
- dose to spinal cord
- volume of treated lung
- baseline lung function and development of fibrosis
Describe RT combined wit chemotherapy
In increasing order of effectiveness
- Radiotherapy alone
- Sequential chemotherapy then radiotherapy
- Combination chemo-radiotherapy
Patient age and co-morbidities determining factor
Cisplatin backbone of chemotherapy in combination with another (etoposide, paclitaxel, vinorelbine)
What is SACT (Systemic Anti-Cancer Therapy)?
Systemic anticancer therapy
- Cytotoxic chemotherapy
- Targeted agents (tyrosine kinase inhibitor)
- Immunotherapy
Indications
- Neo-adjuvant (non standard in UK)
- Adjuvant post surgery (chemo- cisplatin/vinorelbine)
- Adjuvant post chemoRT
- Palliative
Describe EGFR mutations
- EGFR cellular receptor mutations
- ~10% in UK population (40% in SE asia)
- Typically \: young \: female \: non-smoker \: asian
What are the EGFR inhibitor drugs and their side effects?
1st generation
- Gefitinib 250mg OD
- Erlotinib 150mg OD
2nd generation
- Afatinib 40mg OD
3rd generation
- Osimertinib 80mg OD
Side effects
- Diarrhoea
- Acne like skin rash
- Stomatitis
- Paronychia
- Hepatitis
JUST READ
- Lung cancer
- Prognosis from lung cancer remains poor
- Need earlier diagnosis
- Can be treated with surgery, radiotherapy and SACT often in combination
- Metastatic lung cancer can be treated with traditional cytotoxic chemotherapy, targeted drugs (non-smokers with driver mutation) and increasingly immunotherapy
What is a colorectal cancer?
- occurence of malignant lesions in the mucosa of the colon and rectum
- Colorectal cancers are all adenocarcinomas
Describe Bowel wall layers
Mucosa
- epithelium, lamina propria
Submucosa
- rich in lymphatics and blood vessels
Muscularis propria
- circular and longitudinal muscle
Describe Epidemiology of colorectal cancer
- Fourth commonest cancer in UK
- 1 in 14 men, 1 in 19 women will be diagnosed with CRC in their lifetime
- Age - median 60
- Sex 1.5:1 (M:F)
- Geography
: higher in west, diet related
What are the common symptoms of colorectal cancer?
Depends on location
- rectal bleeding
- change in bowel habit
- weight loss
- iron deficiency anaemia
- bowel obstruction
Prognosis: depends on stage, % 5year survival
- Stage 1 = (T1/T2) - 95%
- Stage 2 = (T3/T4) - 84%
- Stage 3 = (Any N) - 62%
- Stage 4 = (M1) - 7%
What are the causes of Colorectal cancer?
- Polyps (small growths on the inner lining of the large intestine (colon) or rectum.)
- Diet, not quite simple.
- Family history
: 1st degree relatives key - IBD
- Genetics Syndrome
- Previous cancer/radiation
- Obesity, smoking, alcohol
What is a Polyp?
Macroscopic description
- protuberant growth from the mucosa
- Benign epithelial tumour of cells derived from glandular epithelium
- all dysplastic and have disregulated proliferation
What are different modes of spreads in colorectal cancer?
Direct
- invades other structures
- e.g bladder, abdominal wall
Lymphatic
- Critical
- Basis of original Dukes staging
- These run with the blood vessels and are a critical aspect of surgery
Haematogenous
- Portal vein to the liver
- 25% CRC patients present with mets
Transcoelomic
- spread throughout the peritoneal cavity
- classically to ovaries
Implantation
- suture line
- wound
- laparoscopic ports sites
What is Dukes Staging in colorectal cancer?
Dukes A
- confined to bowel wall
Dukes B
- through bowel wall
Dukes C
- lymph nodes involved
Dukes D
- Distant metastases
What are the general symptoms of colorectal cancer?
- Anorexia
- Weight loss
- Anaemia
- Fatigue
What are the local symptoms of colorectal cancer?
- Abdominal mass
- Iron deficiency anaemia (IDA)
- Small bowel obstruction
- Perforation
- Symptomless
What is Right-sided symptoms in colorectal cancer?
Right sided
- can grow to a large size before becomes symptomatic as stool soft in right colon and larger diameter
What is left-sided symptoms in colorectal cancer?
- rectal bleeding
- change in bowel habit
- bowel obstruction
- mucus discharge
- fistula: to e.g bladder
- perforation
How is colorectal cancer screened?
Endoscopy
- flexible sigmoidoscopy and colonoscopy
CT colonoscopy
- good sensitivity/specificity
- cannot biopsy
- good for completion ‘scope’ if obstructing tumour/cannot complete endoscopically
What are the common chemotherapeutic drugs in colorectal cancer?
5-Fluorouracil
- interferes with RNa synthesis and DNa replication
Leucovorin
- potentiates 5FU
Oxaliplatin
- cross links DNA, thus inhibits synthesis
Irinotecan
- Topoisomerase inhibitor
Bevacizumab
- VEGF inhibitor
Cetuximab
- EGFR inhibitor
