oncology Flashcards
What is the aetiology of head and neck cancer?
Cigarettes
Alcohol
Lifestyle
Genetics
Virus- HPV
Hormones
Immunosuppression
Premalignant oral conditions (leukoplakia, lichen sclerosis)
Radiotherapy exposure
What are signs of cancer?
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
What is our role (pre-tx assessment)?
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
What are short term tx side effects?
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
What are long term tx side effects?
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
What prevention should be given?
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
What are jaw exercises?
Stack wooden spatulas in mouth 7-8s a day
What are examples of soft tissue reconstruction?
1. Radial forearm flap
2. Antero lateral thigh flap
3. Latissimus dorsi
4. Rectus abdominus
5. Para/scapular axis flap
6. Pedicle tongue flap
What are examples of composite reconstruction?
1. Fibula flap
2. Deep circumflex iliac artery flap
3. Scapular flap
4. RFF
What is the Browns classification?
Horizontal and vertical components measuring extent of defects
What does the success of implants require?
Anchorage and stabilisation
Clot form between implant and osteotomy site
Release of growth factors, angiogenesis and migration of osteoprogenitor cells (deposition of bone)
Why is irradiated bone difficult to place implants?
Biological processes for success may be compromised/absent
Mechanical over biological anchorage
Is viable bone capable of remodelling when loaded
What do tissue changes depend on?
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)
What are haematological issues with chemotherapy?
1. Decreased RBCs- anaemia
2. Decreased WBCs- leukopenia
3. Decreased platelet count- thrombocytopenia
What are popular chemo drugs?
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
When do you treat a cancer pt?
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
What tx may you give to a cancer pt?
1. Extractions + other
2. Dental abscess whilst on chemo
3. ONJ/ORNJ (post)
4. Dentures/prosthesis (post)
What is the classification of cancer?
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
What are tx options for cancer?
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
What is surgery?
Fit for GA
Side effects- functional, cosmetic, risk of anaesthetic
Remove tumour w clear margins
May require further tx on review of histology
What is chemotherapy?
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
What are side effects of chemotherapy?
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
When should you tx pts w chemo?
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
What should you look out for in FBC?
Neutropenia
Neutrophils <1
Thrombocytopenia
Platelets <100
Risk of bleeding
Platelets <30
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
What are more modern targeted agents?
Tyrosine kinase inhibitors
- oral
- eg. Dabrafenib, Sunitinib
Monoclonal antibodies
-IV infusion
- eg. Cetuximab, Trastuzumab
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
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
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
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
What is the tx of metastatic bone disease?
1. Radiotherapy
2. Endocrine tx
3. Chemotherapy
4. Tumour targeted therapy
6. Orthopaedic intervention
7. Analgesics
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
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
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
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
What are the tx modalities of radiotherapy?
X-rays- superficial/mega voltage
Electron tx
Brachytherapy
What is HPV?
DNA virus
72 L1 capsid proteins
Orogenital transmission
Type 16 most common
Who makes the decision for the cancer pt?
Pt
Surgeon
Oncologist
Specialist nurse
Plastic surgeon
Speech and language therapist
Dietician
What investigations are needed for head and neck cancer?
Clinical exam
Blood tests
Exam under anaesthesia
Biopsy
Imaging (MRI/CT/PET)
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
What is the tx of ORNJ?
Surgical debridement
Pentoxyphylline
Hyperbaric oxygen
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
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
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
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
How is there resistance of alkylating agents?
Increased activity of DNA repair enzyme
Increase metabolic inactivation of drug
Decrease influx of drug
What are platinum analogues?
Heavy metals
Form highly reactive platinum complexes
Intra strand cross linking
DNA damage
Inhibits cell proliferation
What is Cisplatin?
Highly bound to plasma protein
Conc in kidney, intestines and testes
Poorly penetrates blood brain barrier
Emesis, nephrotoxicity, peripheral neuropathy, ototoxicity
What are antimetabolites?
Fraudulent substrates for biochem reactions
Substitute normal building blocks of RNA and DNA
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
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
What are vinca alkaloids?
Inhibit tubulin proliferation
Disrupts assembly of microtubules
Mitotic arrest in metaphase
Cell death
What are taxanes?
Enhance tubulin polymerisation
Promotes microtubule assembly in absence of required proteins and guanosine triphophate
Inhibits mitosis/cell division
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
What are hormones and antagonists?
Eg. Glucocorticoids, estrogens, estrogen antagonists
What do bisphosphonates do?
Slow rate of growth of bone crystals
Reduce skeletal events
Lower calcium levels
GI toxicities- N&V, indigestion, oesophagitis, diarrhoea
What needs to be considered w drug combination?
Efficacy
Toxicity
Optimum scheduling
Mechanisms of interaction
Avoidance of arbitrary dose changes
What are some direct oral complications of chemo?
Oral mucositis
Taste dysfunction
Neurotoxicity
Salivary gland dysfunction
TMJ dysfunction
Dentinal hypersensitivity
BRONJ
