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Year 3 Sem 2 > 5. Clinical lectures > Flashcards

5. Clinical lectures Flashcards

1
Q

What are the principles of cancer treatment?

A
  • aim to kill cancer cells, but spare normal cells
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2
Q

What are the recent developments of cancer therapy aiming to maximise therapeutic window?

A
  • refine chemotherapy schedules
  • novel targeted agents
  • better supportive medications
  • immunotherapy
  • tailoring of treatment to individuals
  • response prediction
  • radiotherapy improvements
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3
Q

Describe 3 different Chemotherapy treatment settings

A
  1. 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
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4
Q

Describe Staging of Primary Tumour (T) in Breast cancer

A

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

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5
Q

Describe different staging of Regional Lymph Nodes (N)

A

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

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6
Q

Describe different staging of Metastases (M)

A

Mx
- Not evalulated

M0
- No distant metastases

M1
- Distant metastases

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7
Q

What do you look for on a pathology report of tumour?

breast cancer

A
  • Tumour type
  • Associated DCIS/LCIS
  • Size
  • Grade (1-3)
  • Margins
  • Lymphovascular invasion
  • Nodes
  • ER/PgR/HER2 receptor status
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8
Q

Describe Cell surface receptors

A
  • 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
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9
Q

Describe Cell surface receptors in breast cancer

A
  • 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)
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10
Q

What is Endocrine therapy? (breast cancer)

A
  • 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
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11
Q

What are the examples of Anti HER2 directed therapy drugs? (breast cancer)

A

Trastuzumab

Pertuzumab

Kadcyla

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12
Q

Describe Metastatic disease (breast cancer)

A

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
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13
Q

How is Prostate cancer diagnosed?

A
  • 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
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14
Q

Describe Prostate cancer pathology

A
  • 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
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15
Q

What are Radical treatment options (localised disease) for prostate cancer?

A

Surgery

  • open
  • Laparoscopic
  • Robot-assisted
Radiotherapy
- external beam radiotherapy
\: Conformal
\: IMRT
\: IGRT
- LDR brachytherapy
- HDR brachytherapy

Activev surveillance

Watchful waiting

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16
Q

Describe metastatic Prostate cancer

A
  • 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
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17
Q

What is the cause of Lung cancer?

A

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
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18
Q

What are the two main groups of lung cancer?

A

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
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19
Q

Describe SCLC (Small cell lung cancer)

A
  1. 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
  2. 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
20
Q

What are symptoms and signs of lung cancer?

A 
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)
21
Q

Describe Diagnostic test for lung cancer

A

Bronchoscopy (central)

CT guided lung biopsy (peripheral)

Endobronchial ultrasound (EBUS)

US guided biopsy of neck nodes

Surgical biopsy

22
Q

Describe Diagnostic test: imaging regarding

  • CXR
  • CT
  • PET-CT
A

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
23
Q

Describe Adjuvant chemotherapy in lung cancer

A

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

24
Q

Describe Radiotherapy in lung cancer

A

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
25
Q

What is Stereotactic Ablative Body Radiotherapy (SABR)?

A

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
26
Q

What is Conventional radiotherapy?

A

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
27
Q

Describe RT combined wit chemotherapy

A

In increasing order of effectiveness

  1. Radiotherapy alone
  2. Sequential chemotherapy then radiotherapy
  3. Combination chemo-radiotherapy

Patient age and co-morbidities determining factor

Cisplatin backbone of chemotherapy in combination with another (etoposide, paclitaxel, vinorelbine)

28
Q

What is SACT (Systemic Anti-Cancer Therapy)?

A

Systemic anticancer therapy

  1. Cytotoxic chemotherapy
  2. Targeted agents (tyrosine kinase inhibitor)
  3. Immunotherapy

Indications

  • Neo-adjuvant (non standard in UK)
  • Adjuvant post surgery (chemo- cisplatin/vinorelbine)
  • Adjuvant post chemoRT
  • Palliative
29
Q

Describe EGFR mutations

A
  • EGFR cellular receptor mutations
  • ~10% in UK population (40% in SE asia)
- Typically
\: young
\: female
\: non-smoker
\: asian
30
Q

What are the EGFR inhibitor drugs and their side effects?

A

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
31
Q

JUST READ

- Lung cancer

A
  • 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
32
Q

What is a colorectal cancer?

A
  • occurence of malignant lesions in the mucosa of the colon and rectum
  • Colorectal cancers are all adenocarcinomas
33
Q

Describe Bowel wall layers

A

Mucosa
- epithelium, lamina propria

Submucosa
- rich in lymphatics and blood vessels

Muscularis propria
- circular and longitudinal muscle

34
Q

Describe Epidemiology of colorectal cancer

A
  • 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
35
Q

What are the common symptoms of colorectal cancer?

A

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%
36
Q

What are the causes of Colorectal cancer?

A
  • 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
37
Q

What is a Polyp?

A

Macroscopic description
- protuberant growth from the mucosa

  • Benign epithelial tumour of cells derived from glandular epithelium
  • all dysplastic and have disregulated proliferation
38
Q

What are different modes of spreads in colorectal cancer?

A

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
39
Q

What is Dukes Staging in colorectal cancer?

A

Dukes A
- confined to bowel wall

Dukes B
- through bowel wall

Dukes C
- lymph nodes involved

Dukes D
- Distant metastases

40
Q

What are the general symptoms of colorectal cancer?

A
  • Anorexia
  • Weight loss
  • Anaemia
  • Fatigue
41
Q

What are the local symptoms of colorectal cancer?

A
  • Abdominal mass
  • Iron deficiency anaemia (IDA)
  • Small bowel obstruction
  • Perforation
  • Symptomless
42
Q

What is Right-sided symptoms in colorectal cancer?

A

Right sided

- can grow to a large size before becomes symptomatic as stool soft in right colon and larger diameter

43
Q

What is left-sided symptoms in colorectal cancer?

A
  • rectal bleeding
  • change in bowel habit
  • bowel obstruction
  • mucus discharge
  • fistula: to e.g bladder
  • perforation
44
Q

How is colorectal cancer screened?

A

Endoscopy
- flexible sigmoidoscopy and colonoscopy

CT colonoscopy

  • good sensitivity/specificity
  • cannot biopsy
  • good for completion ‘scope’ if obstructing tumour/cannot complete endoscopically
45
Q

What are the common chemotherapeutic drugs in colorectal cancer?

A

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

Year 3 Sem 2 (12 decks)

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