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Oncology, pharmacology, anaesthetics (IHD DEN303) > Clinical oncology > Flashcards

Clinical oncology Flashcards

1
Q

Cancer definition

A

Group of diseases characterised by uncontrolled growth and spread of abnormal cells within a body

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2
Q

Oncology/ oncologists

A

Specialism/ specialists in cancer

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3
Q

How many cancers?

A

Around 200

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4
Q

Classification of cancers

A 
Type of cancer cell
-glandular e.g. adenocarcinoma
-skin/ mucosa e.g. squamous cell carcinomoma
-connective tissues e.g. sarcoma
-small cell e.g. small cell carcinoma
Grade (degree of differentiation usually G1-G3)
TNM staging
-size of tumour
-spread to lymph nodes
-spread to distal organs
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5
Q

Prognostic makers to determine treatment pathways

A

E.g.

  • oestrogen receptor (ER) in breast cancer
  • HER2 receptor in breast cancer
  • BRAF mutation in melanoma
  • HPV association in head and neck cancer
  • EGFR expression in lung cancer
  • PSA level in prostate cancer
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6
Q

How common is cancer?

A

1 in 3 lifetime risk

Increasing incidence for several types

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7
Q

Incidence of oral cavity cancer

A

Males higher than females

  • males ~11/100,000
  • females ~7/100,000
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8
Q

Risk factors for head and neck cancer

A 
Smoking
Alcohol
Diet and nutrition
Viruses
-HPV
-Epstein Barr Virus
Immunosuppression
Premalignant oral conditions
-leukoplakia
-lichen sclerosis
Radiotherapy exposure
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9
Q

Risk factors for colorectal cancer

A

Dietary

Genetic

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10
Q

Risk factors for lung cancer

A

Smoking

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11
Q

Risk factors for breast cancer

A

Genetic

Obesity

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12
Q

Risk factors for skin cancer

A

Sun exposure

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13
Q

Risk factors for cervical cancer

A

HPV

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14
Q

Changes in incidence of oral cancer

A

Men over 80: incidence of OC more than halved since 1975
Men in 70’s: rates remained relatively stable
Large > in incidence of OC diagnosed in men in 40s & 50s: rates more than doubled

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15
Q

Improved survival

A 
Earlier diagnosis
- > pt awareness (media, internet)
-screening programs (colorectal, breast, prostate, ovary, cervix)
Improved treatment
-surgery
-radiotherapy
-chemotherapy
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16
Q

Treatment options

A
  1. Surgery
  2. Radiotherapy
  3. Chemotherapy
  4. Hormonal therapy
  5. Targeted therapies
  6. Immunotherapy
  7. Laser therapy
  8. Cryotherapy
  9. Best supportive care
  10. Any combination of these
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17
Q

Surgery

A

Can be curative treatment on its own for many cancers
Usually need to be fit for GA
Aims to remove tumour with clear margins
May require further treatment on review of histology
-adjuvant chemotherapy/ hormones
-adjuvant radiotherapy

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18
Q

Side effects of surgery

A

Functional
Cosmetic
Risks of anaesthetic

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19
Q

Chemotherapy

A

The use of cytotoxic drugs to kill malignant cells
Systemic treatment: IV, PO or IT
Can be given in more localised way for certain tumour types e.g. intravesical to treat superficial bladder cancer
Drugs which affect cell function
Drugs often used in combination in increase effect
Anti cancer action in expense of side effects

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20
Q

Different mechanisms of action of chemotherapy

A 
Platinum
-cisplatin/ carboplatin/ oxaliplatin
Taxanes
-docetaxel/ paclitaxel
Anti metabolites
-5 fluorouracil/ methotrexate
Alkylating agents
-dacarbazine/ temozolamide
Anthracyclines
-doxorubicin/ epirubicin
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21
Q

Chemotherapy adjuvant treatment

A

High risk post op pts
Often combination of drugs - more side effects
Given chemo to < risk of recurrence
-pt may not have disease and not need it
-pt may get recurrence despite chemo
-proportion (5-10%) will be cured because of it
-need to assess risks vs benefits with pt carefully

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22
Q

Chemotherapy -palliative treatment

A

Treatment to improve symptoms and maybe extend life
Often single drug
- < side effects
-lower intensity of treatment
Not usually offered until symptomatic
Stop early if not working or increasing toxicity

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23
Q

Chemo side effects

A 
General
-nausea and vomiting
-fatigue
-change in taste
-bowel disturbance
Skin
-rash
-hair loss
-extravasation
Nerves
-neuropathy
-hearing loss
Infertility/ premature menopause
Bone marrow
-anaemia
-neutropenia
-thrombocytopenia
Renal dysfunction
Liver dysfunction
Allergic reaction/ anaphylaxis
Lung toxicity
-fibrosis
-bleomycin
Cardiac toxicity
-cardiomyopathy
-anthycyclines
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24
Q

More modern targeted agents

A 
Tyrosine kinase inhibitors (oral)
-Vermurafenib (BRAF mutation melanoma)
-Gefinitinib
-Imatinib 
-Sunitinib
Monoclonal antibodies (IV infusion)
-Trastuzumab (HER2 receptor breast cancer)
-Cetuximab
-bevacuizumab
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25
Q

Radiotherapy

A

Radium used until mid 1900s
-cobalt and caesium units came into use
Linear accelerators been used since late 1940s
The use of ionising radiation to treat cancer

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26
Q

Radiotherapy

-therapeutic vs diagnostic

A

Energy of photos higher in therapeutic setting as opposed to diagnostic setting

  • diagnostic x-rays up to 150KV
  • therapeutic photons 80KV to 20MV
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27
Q

How does radiotherapy work?

A

Ionising radiation interacts with water molecules –> free radicals
Free radicals cause DNA damage
Malignant and normal cells are damaged
Normal cells can repair if tolerance not exceeded

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28
Q

Side effects of radiotherapy

A 
Damage to normal cells
-depend on area to be treated
-divided into early or late effects
Early (acute)
-develop during or shortly after RT
-very common
-nearly always resolve
Late (chronic)
-develop months to years (>40yrs) after RT
-very rare
-irreversible and often severe
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29
Q

Intention of radiotherapy

A 
Radical - curative
Palliative - to improve symptoms
Adjuvant - alongside surgery
Neoadjuvant - before surgery
Alone - single modality
Combined with chemo - can sensitise tissues to radiotherapy
*Local treatment
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30
Q

Dose and number of radiotherapy treatments (fractions) depends on

A

Area being treated

Intention of treatment - curative vs palliative

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31
Q

Curative radiotherapy

A 
Complex planning
Accurate localisation - CT
Longer course 
More early side effects
Less late side effects
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32
Q

Palliative radiotherapy

A 
Simple planning
Simple localisation - X-ray
Short course
Less early side effects
More late side effects
33
Q

Radiotherapy treatment modalities

A 
X-rays
-superficial radiotherapy
-megavoltage radiotherapy 6-20MV
Electron treatment 6-20MeV
Bracytherapy: insertion of isotopes into tumour
34
Q

Superficial radiotherapy

A

100KV photons
Treats to depth of 6mm
Good for superficial BCC and SCC

35
Q

Megavoltage x-rays and e- treatment

A

The linear accelerator

36
Q

CT planned radiotherapy

A

Less dose to underlying structures

Less toxicity?

37
Q

Stereotactic radiosurgery

A

Brain metastasis
- <3 lesions of 3cm size
Single treatment of high dose

38
Q

Types of head and neck cancer

A 
Oral cavity
-floor of mouth
-anterior 2/3 tongue
-alveolus
-retromolar trigone
-hard palate
Nasopharynx
Oropharynx
Larynx
-supraglottis/ glottis/ post cricoid
Hypopharynx
Sinuses
39
Q

Pathology of head and neck cancer

A 
Squamous cell cancer 90% (arising from mucosa)
Adenocarcinoma
Small cell carcinoma
Sarcoma
Lymphoma
Skin
-SCC
-BCC
-malignant melanoma
-merkel cell tumour
40
Q

Demographics of head and neck cancer

A

Males > females 2:1
Peak incidence 60-75 years
Mortality: 3000 deaths/ year in England and Wales

41
Q

Human Papilloma Virus

A

DNA virus
72 L1 capsid proteins
Orogenital transmission
Cervical and oropharyngeal SCC type 16 most common

42
Q

HPV in head and neck cancer

A

+ve in approx 25%
Distinct disease entity
-younger pts
-40s to 50s
Often not smokers or heavy alcohol drinkers
Associated with orogenital and oroanal sex and > no. partners
HPV related cancer (particularly H&N) definitely on the rise
Improved response to chemoradiation
-28% < risk of dying
-49% < risk of local recurrence

43
Q

Patterns of spread

A 
Locally
-soft tissues
-cartilage
-bone
-nerves
Lymph nodes
-very common esp. nasopharynx and oropharynx
Vascular 
-to lungs, bone and liver occurs late
44
Q

How is the decision made about treatment for an individual pt and their cancer?

A 
Multidisciplinary approach
Need to know
-type of cancer
-stage of cancer
-fitness of pt
-pt's wishes
-functional outcomes for treatments/ side effects of treatments/ is it curative etc
45
Q

Decision making

A

Should happen in joint clinic

  • surgeon
  • oncologist
  • specialist nurse
  • plastic surgeon
  • speech and language therapist
  • dietician
  • (psycology input)
46
Q

Investigations needed:

A 
Clinical examination
Blood tests
Examination under anaesthesia
Biopsy
Imaging
-of primary (MRI, CT scan)
-potential sites of metastatic disease (FDG-PET scan, CT scan thorax/CXR)
47
Q

Other investigations

A

Bone scan
CT/ MRI scan of brain
Angiograms
etc

48
Q

General management principles of early stage disease

A

Can be treated with either surgery or Radiotherapy
Choice of treatment largely depends upon functional outcome and patient choice
Surgery allows review of tumour, margins and lymph node status
Cancer involving cartilage or bone is best treated with surgery

49
Q

General management principles of locally advanced disease

A

Surgery followed by Chemoradiotherapy
Chemoradiotherapy alone
Induction Chemotherapy followed by Chemoradiotherapy

50
Q

General management principles of metastatic disease

A

Palliative Radiotherapy
Palliative Chemotherapy
Best supportive care

51
Q

Non-surgical oncology for H&N cancer

A

Radiotherapy
Chemotherapy
Targeted therapy
-organ preservation: primary treatment
-used alongside surgery to > chance of cure (adjuvant treatment)
-often combined together: multimodality therapy

52
Q

Head and neck radiotherapy

A

Critical structures close e.g. spinal cord, optic chiasm, eyes & brain
Essential to keep pt v still & reproduce same position each day of treatment
Pt often needs to be immobilised using head shell
Pt then has CT scan in head shell
CT is used to mark on:
-areas to be treated
-target volumes
-organs at risk
CT used to produce radiotherapy plan: radiotherapy prescription
Verification process
Pt then goes on to have their treatment
Dose & number of treatments depends on site to be treated and treatment intent
-may be daily treatments for up to 7 weeks if curative
-may be single dose if palliative

53
Q

Verification process (radiotherapy)

A

Pt then goes to machine called simulator for verification
Treatment check
‘Simulator’ is x-ray machine which can move in same way as treatment machine
Simulates treatment
X-rays taken by simulator to check treatment can be reproduced accurately
Pt position verified

54
Q

Early side effects of head and neck radiotherapy

A 
Xerostomia
Altered/loss of taste
Mucositis
Loss of hair
Fatigue
Cough 
Soreness of skin
-dry desquamation
-moist desquamation
55
Q

Late side effects of head and neck radiotherapy

A 
Xerostomia
Altered taste
Osteo-radionecrosis
Alopecia
Hypothyroidism 
Sub-cutaneous fibrosis
Second malignancy
Altered pigmentation
56
Q

Effects of radiotherapy on oral cavity

A 
Xerostomia accelerates dental decay
Osteo-radionecrosis of the mandible 
-associated with poor dental hygiene
Pre-treatment dental assessment essential
-for necessary treatment
-education 
-on going care
Some ps require dental clearance
-issues with treatment start date
57
Q

Radiotherapy technology

A 
Developing Rapidly
More accurate delivery
Dose escalation
Less toxicity
Greater monitoring during treatment
Progress
-conformal 3D radiotherapy
-IMRT
-rotational treatment (Rapid Arc)
-robotic mounted treatment machines (Cyberknife)
58
Q

Chemotherapy in head and neck cancer

A

Concurrent Chemradiotherapy
-Cisplatin every 3 weeks during Radiotherapy
Induction Chemotherapy
-Combination Cisplatin based chemotherapy prior to Radiotherapy for fit patients with bulky tumours
-Docetaxel/ Cisplatin// 5FU (TPF) x3 every 3 weeks
Palliative chemotherapy
-Cisplatin and 5FU every 4 weeks

59
Q

Early side effects of chemotherapy

A 
Alopecia
Bone marrow toxicity
-neutropenia
-thrombocytopenia
-anaemia
Mucositis
Diarrhoea
Nausea/vomiting
Peripheral Neuropathy
Ototoxicity 
Altered taste
60
Q

Late effects of chemotherapy

A 
Infertility
Early menopause
Pulmonary fibrosis
Renal impairment
Cardiomyopathy
Infertility
Peripheral neuropathy
Second malignancy
61
Q

Dentists and oncology

A 
Diagnosis of oral cavity tumours
Health promotion
Dental assessment pre-treatment	
-RT, chemotherapy, bisphosphonates
Pts receiving chemo may require dental work
-abscess 
-beware neutropenia &amp; thrombocytopenia
-may need to ask oncologists opinion
Post treatment follow up
Screening for oral cancer
Maxillo-facial surgeons
Restorative dentists
62
Q

General rule for dental treatments while on chemotherapy

A

Preferably all urgent dental work to be done before commencing chemo
-above not practical for all as treatment needs to start asap to improve outcomes
If already on chemo:
-find out length of cycle
-in 3 weekly cycle (most common) max risk of immuno-suppression between 7014 days
-best to always check FBC prior to urgent dental tx to ensure not neutropenic or low platelets

63
Q

Timing for dental work while on chemo

A 
General rule: avoid if not urgent
In 3 weekly cycle, counts usually are recovering in 3rd week
So just before next cycle is due
Always check FBC prior
Neutropenia is Neuts <1.0
Thrombocytopenia is platelets <100
RIsk of bleeding if platelets <20/ 30
64
Q

Dental abscess in immunocompromised pt

A

Usually on neutropenic sepsis protocol with IV antibiotics and other supportive measures
Unlikely dental abscess is only source of infection
If no other source identified and sepsis not improving with above measures
-draining of abscess recommended
-can have platelet transfusion if low with GCSF cover

65
Q

Dental work for pts on targeted treatments

A

Usually not immunosuppresed if on targeted treatments per se
Risk of infection significant
Check FBC prior to procedure and consider antibiotic cover
Always check with relevant oncologist if treatment necessary

66
Q

Immunotherapy

A

Now in use for most cancers in different settings
PDL1 inhibitors - Pembrolizumab
Immune checkpoint inhibitors - Nivolumab
Can cause ‘itis’ of any organ that can be fatal
Can also be effective in controlling cancers and in % of pts provide sustained benefit for many months/ years

67
Q

Bone treatments in cancer

A

Can be used in adjuvant or palliative setting
Either to < risk of SREs or < symptoms from SREs
Bisphosphonates
RANK ligand inhibitors
Radium 223

68
Q

Metastatic bone disease

A

> bone resorption is hallmark

  • tumour cells release growth factors and cytokines
  • osteoclastic resorption stimulated (peptides e.g. TGF-beta released by bone resorption, tumour cell production of factors increased)
  • **
69
Q

Pharmacokinetic properties of bisphonsphonates

A

1/2 life of circulating bisphosphonate is short - around 0.5-2hrs in humans
Approx 50% of circulating bisphosphonate taken up by skeleton
Rate of uptake by bone very fast
Bisphos can remain in bone from 1-10 years in humans
Are liberated from skeleton during osteoclast resorption

70
Q

Side effects of bisphosphonates

A

Oral therapy

  • upper GI inflammation
  • diarrhoea and abdo pain
71
Q

Safety profile of IV bisphosphonates

A

Mild to moderate flu-like symptoms occur after initial infusions
-generally manageable with paracetamol (acetaminophren)
Dose/ infusion rate-dependent effects on renal function
-clinically relevant serum creatinine > are uncommon (<10%) and generally reversible
ONJ is uncommon event that has been reported in pts with cancer receiving complex treatment reigmens, including IV bisphonates (primarily in pts with advanced malignancies and skeletal metastases)

72
Q

ONJ

A

<1%
Probably related to potency and duration of treatment
Probably more common with IV formulations
About 1% per year of treatment on IV pamidronate/ zoledronic acid
Largely preventable with good dental care

73
Q

What do we know about ONJ and risk management?

A

Spontaneous reports primarily in pts with advanced cancer and bone mets

  • freq. estimates vary but <1%
  • etiology and pathogenesis poorly understood
74
Q

Recommendations for minimising ONJ risk

A

Consider dental exam with appropriate preventative dentistry before BP tx
Avoid invasive dental procedures if possible during tx
For pts requiring dental procedures, no data to suggest whether discontinuation of BPs < risk of ONJ

75
Q

In case of ONJ

A

Reassess benefit/ risk of continued BP therapy
Discuss options with pts
Manage conservatively
Note that healing of lesions has been reported in most cases

76
Q

General rule for dental treatments of pts on bisphosphonates

A

Pre-assessment prior to starting BPs or Denosumab mandatory
Prevention vital
While on BPs or Denosumab:
-at onset of symptoms suspend Rx until dental assessment to exclude any suspicion of ONJ
-if not ONJ, restart after 6 weeks of dental work
-if ONJ, suspend or stop indefinitely (discuss risk/ benefit with pt)

77
Q

Denosumab advantages

A

Given SC, more convenient than IV Zoledronate
No concerns about renal safety, so no renal monitoring required
Fewer acute-phase reactions

78
Q

ONJ zoledronic acid vs denosumab

A

Similar BUT Denosumab expensive

79
Q

Denosumab side effects

A 
Back pain
Arm and leg pain
High cholesterol
Muscle pain
Bladder infection
Hypocalcaemia - prescribe calcium and vit D

Oncology, pharmacology, anaesthetics (IHD DEN303) (6 decks)

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