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oncology Flashcards

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1
Q

What is the aetiology of head and neck cancer?

A

Cigarettes
Alcohol
Lifestyle
Genetics
Virus- HPV
Hormones
Immunosuppression
Premalignant oral conditions (leukoplakia, lichen sclerosis)
Radiotherapy exposure

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2
Q

What are signs of cancer?

A

Non healing ulcer/swelling/sore (indurated or hard margin)
Red/white patches
Loose teeth
Jaw pain
Lump, bump, mass w or w/o pain
Persistent sore throat
Foul mouth odour
Hoarseness/change in voice (>6 weeks)
Pain in mastication
Dentures no longer fit

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3
Q

What is our role (pre-tx assessment)?

A

1. Avoid unscheduled interruptions
2. Pre-prosthetic planning/tx
3. Plan x of teeth (prognosis/risk)
4. Extract (10 days prior radiotherapy)
5. Plan for remaining teeth
6. Preventative advice/tx

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4
Q

What are short term tx side effects?

A

Mucositis- 2-4 weeks after radiotherapy
~ice chips, difflam, SLS free toothpaste

Infection- chemo induced neutropenia- oral Candida v common

Xerostomia- radiotherapy damages salivary gland

Ageusia- avoid sweet/sour

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5
Q

What are long term tx side effects?

A

Altered anatomy

Rampant dental caries- diet, reduced saliva, radiogenic damage to ADJ

Trismus- surgical scarring/radiogenic fibrosis of MofM

Mastication difficulties- tooth loss

Life long osteoradionecrosis- hypovascularity and necrosis of bone, mucosal breakdown, non healing wound

Xerostomia- challacombe scale

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6
Q

What prevention should be given?

A

1. Good OH
2. Diet advice
3. Daily 5000ppm fluoride w GC tooth mouse in custom tray
4. Saliva substitute (NOT glandosane- high acidity)
5. Jaw exercises

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7
Q

What are jaw exercises?

A

Stack wooden spatulas in mouth 7-8s a day

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8
Q

What are examples of soft tissue reconstruction?

A

1. Radial forearm flap
2. Antero lateral thigh flap
3. Latissimus dorsi
4. Rectus abdominus
5. Para/scapular axis flap
6. Pedicle tongue flap

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9
Q

What are examples of composite reconstruction?

A

1. Fibula flap
2. Deep circumflex iliac artery flap
3. Scapular flap
4. RFF

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10
Q

What is the Browns classification?

A

Horizontal and vertical components measuring extent of defects

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11
Q

What does the success of implants require?

A

Anchorage and stabilisation
Clot form between implant and osteotomy site
Release of growth factors, angiogenesis and migration of osteoprogenitor cells (deposition of bone)

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12
Q

Why is irradiated bone difficult to place implants?

A

Biological processes for success may be compromised/absent
Mechanical over biological anchorage
Is viable bone capable of remodelling when loaded

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13
Q

What do tissue changes depend on?

A

1 Dose (depends on stage/grade of cancer)

2. Mode of therapy (conventional/intensity modulated RT/brachytherapy)

3. Intensity modulated therapy (multiple, non-uniform intensity, limits dose to normal tissue)

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14
Q

What are haematological issues with chemotherapy?

A

1. Decreased RBCs- anaemia

2. Decreased WBCs- leukopenia

3. Decreased platelet count- thrombocytopenia

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15
Q

What are popular chemo drugs?

A

1. Cisplatin- cytotoxic drug damages DNA and inhibits DNA synthesis

2. Fluoropyrimidines (eg. 5-fluorouracil)- increases radiation sensitivity in cancer cells

For other cancers
1. Monoclonal antibodies eg Ritixumab
2. Bisphosphonates
3. Anti angiogenic biological therapies eg. Sunitinib

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16
Q

When do you treat a cancer pt?

A

All active tx during cancer tx- oncology/haem team

If chemotherapy in last 6 months- seek advice from team and avoid non essential

Invasive may be provided IF
-radiotherapy to areas other than head and neck
-chemotherapy more than 6 months ago
-biological/hormonal therapies

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17
Q

What tx may you give to a cancer pt?

A

1. Extractions + other
2. Dental abscess whilst on chemo
3. ONJ/ORNJ (post)
4. Dentures/prosthesis (post)

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18
Q

What is the classification of cancer?

A

Glandular=adenocarcinoma
Skin/mucosa=sqamous cell carcinoma
C. Tissue= sarcoma
Small cell= small cell carcinoma
Lymph node= lymphoma

Grade (G1-3)

T= size
N= spread to lymph nodes
M= spread to distal organs

Prognostic markers to determine tx pathways eg. HPV association (p16) in head and neck cancer

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19
Q

What are tx options for cancer?

A

1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Hormonal therapy
5. Targeted therapies
6. Immunotherapy
7. Laser therapy
8. Cryotherapy
9. Best supportive care

ANY COMBINATION

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20
Q

What is surgery?

A

Fit for GA
Side effects- functional, cosmetic, risk of anaesthetic
Remove tumour w clear margins
May require further tx on review of histology

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21
Q

What is chemotherapy?

A

Drugs affect cell function
Often used in combination

Platinum (Cisplatin, carboplatin etc)
Taxanes (Docetaxel, Paclitaxel etc)
Antimetabolites (5-fluorouracil, methotrexate)
Alkylating agents (Dacarbazine, Temozolamide)
Anthracyclines (Doxorubicin, Epirubicin)

Adjuvant- high risk post op pts, reduce risk of reoccurrence
-5-10% cured as a result, tx carries risks, risks vs benefits

Palliative- improve symptoms and extend life, single drug, less side effects/intensity

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22
Q

What are side effects of chemotherapy?

A

N&V
Fatigue
Change in taste
Bowel disturbance
Rash
Hair loss
Neuropathy
Hearing loss
Infertility
Premature menopause
Renal/liver dysfunction
Allergy
Lung/cardiac toxicity
Bone marrow problems

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23
Q

When should you tx pts w chemo?

A

Preferably all urgent before

If already on-
-find out length of cycle
-3 weekly cycle- maximum risk of suppression 7-14 days- so do just before next cycle
- always check FBC prior

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24
Q

What should you look out for in FBC?

Study These Flashcards
A

Neutropenia
Neutrophils <1

Thrombocytopenia
Platelets <100

Risk of bleeding
Platelets <30

25
What should you do with a dental abscess in an immunocompromised pt?
Usually neutropenic sepsis protocol w IV antibiotics etc Unlikely only source of infection If no other source found and sepsis not improving- drain, can have platelet transfusion of low w GCSF cover
26
What are more modern targeted agents?
Tyrosine kinase inhibitors - oral - eg. Dabrafenib, Sunitinib Monoclonal antibodies -IV infusion - eg. Cetuximab, Trastuzumab
27
When should you tx pts w targeted tx?
Usually not immunosuppressed Risk of infection significant Check FBC and consider antibiotic cover Always check w oncologist if tx necessary
28
What is immunotherapy?
PDL1 inhibitors Eg. Pembrolizumab Immune checkpoint inhibitors Eg. Nivolumab Can cause itis of any organ- fatal Can control cancers and sometimes benefit for years
29
What are bone tx in cancer?
Adjuvant/palliative Bisphosphonates, RANK ligand inhibitors, Radium 223 Increased bone resorption is hallmark of metastatic bone disease- osteoclast key target
30
What is the cycle of bone destruction?
1. Tumour cells release growth factors and cytokines (RANK ligand overexpression) 2. Osteoclastic resorption stimulated 3. Peptides released by resorption 4. Tumour cell production of factors increased 5. Tumour cell proliferation 6. More bone resorption
31
What is the tx of metastatic bone disease?
1. Radiotherapy 2. Endocrine tx 3. Chemotherapy 4. Tumour targeted therapy 6. Orthopaedic intervention 7. Analgesics
32
What is the effect of bisphosphonates on the cycle of bone destruction?
1. Decrease activity of osteoclasts 2. Less peptide release 3. Slowed tumour cell growth 4. Reduced production of factors 5. Decrease in bone resorption
33
What are side effects of bisphosphonates?
Oral -upper GI inflam -diarrhoea and ab pain IV -fever and myalgia (temporary) -electrolytes and mineral adverse events -rare renal toxicity -risk of ONJ
34
What is the effect of Denosumab on the cycle of bone destruction?
1. Binds to RANK ligand 2. Inhibits osteoclast formation, function and survival Given subcutaneous No renal safety concerns Fewer acute reactions Side effects- back/arm/leg/muscle pain, high cholesterol, bladder infection, hypocalcaemia
35
What is radiotherapy?
Ionosing radiation interacts w water molecules to create free radicals which cause DNA damage Normal and malignant cells damaged Normal can repair if tolerance not exceeded Energy of photons is higher in therapeutic over diagnostic Diagnostic- >150kV Therapeutic- 80kV-20mV Radical/adjuvant/palliative/neoadjuvant
36
What are the tx modalities of radiotherapy?
X-rays- superficial/mega voltage Electron tx Brachytherapy
37
What is HPV?
DNA virus 72 L1 capsid proteins Orogenital transmission Type 16 most common
38
Who makes the decision for the cancer pt?
Pt Surgeon Oncologist Specialist nurse Plastic surgeon Speech and language therapist Dietician
39
What investigations are needed for head and neck cancer?
Clinical exam Blood tests Exam under anaesthesia Biopsy Imaging (MRI/CT/PET)
40
What are side effects of head and neck radiotherapy?
EARLY Xerostomia Altered/loss of taste Mucositis Loss of hair Fatigue Cough Soreness of skin LATE Xerostomia Altered taste ORNJ Alopecia Hypothyroidism SC fibrosis Second malignancy Altered pigmentation
41
What is the tx of ORNJ?
Surgical debridement Pentoxyphylline Hyperbaric oxygen
42
What is the log kill hypothesis?
Chemo drugs kill a constant proportion of cells rather than a constant no of cells So solid tumours have a poor response whereas disseminated cancers respond well
43
How is the cell cycle involved?
CCS- drugs that act on cell cycle Eg. Antimetabolites, taxanes, vinca alkaloids) CCNS (cell cycle non specific)- drugs that sterilise tumour cells whether they’re cycling or resting in the G0 compartments Eg. Alkylating agents, platinum analogs
44
What are examples of chemo drugs?
CSS 5-fluorouracil (S phase) pyrimidinr analogue Methotrexate (S phase) folic acid analogue Vinblastine (M phase) CCNS Decarbazine Busulfan Cisplatin
45
What are alkylating agents?
Highly reactive carbonium ion Transfer alkyl groups to nucleophilic sites on DNA bases Cross linkage, abnormal base pairing, DNA strand breakage 6 major chemical classes Increase risk of secondary malignancies Bone marrow depression, N&V
46
How is there resistance of alkylating agents?
Increased activity of DNA repair enzyme Increase metabolic inactivation of drug Decrease influx of drug
47
What are platinum analogues?
Heavy metals Form highly reactive platinum complexes Intra strand cross linking DNA damage Inhibits cell proliferation
48
What is Cisplatin?
Highly bound to plasma protein Conc in kidney, intestines and testes Poorly penetrates blood brain barrier Emesis, nephrotoxicity, peripheral neuropathy, ototoxicity
49
What are antimetabolites?
Fraudulent substrates for biochem reactions Substitute normal building blocks of RNA and DNA
50
What is methotrexate?
Binds to active catalytic site of DHFR Inhibits synthesis of THF Interferes w formation of DNA, RNA and cellular proteins Cytotoxic, immunosuppressive and anti inflam Side effects- megaloblastic anaemia, leukopenia, alopecia, nephropathy
51
What is 5 fluorouracil?
Activation via complex series of enzymatic reactions Between ribosyl and deoxirybosil nucleotide metabolites 5-10 min half life Side effects- N&V, headache, mood disorder, cardiotoxicity, GI problems, vein pigmentation, local pain, dermatitis
52
What are vinca alkaloids?
Inhibit tubulin proliferation Disrupts assembly of microtubules Mitotic arrest in metaphase Cell death
53
What are taxanes?
Enhance tubulin polymerisation Promotes microtubule assembly in absence of required proteins and guanosine triphophate Inhibits mitosis/cell division
54
What are anti tumour antibiotics?
Bind to DNA through intervals toon between specific bases Blocks synthesis of RNA and DNA, DNA strand scission, interfere w cell replication Eg. Bleomycin, doxorubicin
55
What are hormones and antagonists?
Eg. Glucocorticoids, estrogens, estrogen antagonists
56
What do bisphosphonates do?
Slow rate of growth of bone crystals Reduce skeletal events Lower calcium levels GI toxicities- N&V, indigestion, oesophagitis, diarrhoea
57
What needs to be considered w drug combination?
Efficacy Toxicity Optimum scheduling Mechanisms of interaction Avoidance of arbitrary dose changes
58
What are some direct oral complications of chemo?
Oral mucositis Taste dysfunction Neurotoxicity Salivary gland dysfunction TMJ dysfunction Dentinal hypersensitivity BRONJ

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