Clinical Oncology I Flashcards
Dentists involvement in oncology?
Diagnose oral cavity tumours
Health promotion
Dental assessment pre-tx:
- RT, chemo, bisphosphonates, denosumab
Pt receiving cancer tx may require dental work:
- Extractions - when is best time to do tx
- Dental abscesses on chemo
- Immunocompromised pt
- Dental problems 2ndry to cancer tx - bronj
- Dentures/prostheses post cancer tx
Case 1
Come back before 2nd cycle of chemo for the procedures
Case 2: Acute dental pain
Zoledronate = bisphosphonate
Check it’s not osteo-necrosis
Likely diagnosis = BRONJ
Case 3: Colon cancer
Dental abscess
Low neutrophil count (as below 1)
On chemo
Neutropenic sepsis
Case 4: Smoked recently diagnosed with T4N2b base of tongue squamous cell cancer
Comes to you for dental assessment prior to RT planning
Cancer is curative with RT
Do not start dental tx during RT:
- Radionecrosis
- Xerostomia
Case 5: Tonsil cancer invading soft palate
Pt refuses dental tx
Treated her cancer without dental tx
Define cancer
Group of diseases characterised by uncontrolled growth and spread of abnormal cells within a body
How to classify cancer?
Type of cancer:
- Glandular = adenocarcinoma
- Skin/mucosa = squamous cell carcinoma
- CT = sarcoma
- Small cell = small cell carcinoma
- Lymph nodes = lymphoma
Grade - degree of differentiation usually G1-3
TNM staging:
T = size of tumour
N = Spread to lymph nodes
M = spread to distal organs
What prognostic markers are used to determine tx pathways?
Oestrogen receptor (ER) in Breast cancer HER2 receptor in Breast cancer BRAF mutation in melanoma HPV association in head and neck cancer EGFR expresson in lung cancer PSA level in Prostate cancer
Incidence of oral cavity cancer
Is increasing
Risk factors for cancer?
Lung - smoking Breast - genetic, obesity Skin - Sun exposure Cervix - Human papilloma virus Head and neck: - Smoking - Alcohol - Diet and nutrition - Viruses - HPV, EBV - Immunosuppression - Premalignant oral conditions (leukoplakia, lichen sclerosis) - Radiotherapy exposure
How to improve cancer survival?
Earlier diagnosis - increased pt awareness - screening programmes: colorectal, breast, prostate, ovary, cervix Improved tx: - surgery - RT - Chemo
Tx options for cancer?
Surgery RT Chemo Hormonal therapy Targeted therapies Immunotherapies Laser therapy Cryotherapy Best supportive care Any combo of these
Surgery features?
Can be curative tx
Usually need to be fit for GA
Side effects - functional, cosmetic, risk of anaesthetic
Aim to remove tumour with clear margins
May require further tx on review of histology - adjuvant chemo/hormones, adjuvant RT
Chemo features?
Drugs which affect cell function Drugs often used in combo to increase effect Different mechanisms: - Platinum - Taxanes - Anti-metabolites (methotrexate) - Alkylating agents - Antracyclines
Chemo adjuvant tx features?
High risk post op pts
Often a combo of drugs - more side effects
Given chemo to reduce risk of recurrence:
- Pt may not have disease and not need it
- Pt may get recurrence despite chemo
- But a proportion will be cured bcos of it (5-10%, tx carries risks, need to assess and discuss with pt, risks vs benefits)
Chemo palliative tx features?
Tx to improve symptoms and maybe extend life
Often single drug - fewer side effects, lower intensity of tx
Not usually offered until symptomatic
Stop early if not working or increasing toxicity
Chemo side effects?
General: - Nausea and vomiting - Fatigue - Change in taste - Bowel disturbance Skin: - Rash - Hairloss
Nerves:
- Neuropathy
- Hearing loss
Infertility
Bone marrow: - Anaemia - Neutropenia - Thrombocytopenia Renal and liver dysfunction Allergic rxn Lung toxicity - fibrosis Cardiac toxicity - cardiomyopathy
Give examples of modern targeted agents?
Tyrosine kinase inhibitors
Oral
Vemurafenib - BRAF mutation in melanoma
Gefitinib - EGFR mutation in Lung Cancer
Imatinib - c-Kit CML/GIST
Sunitinib - PDGF/VEGF in Renal/Sarcoma/
Monoclonal antiobodies
IV infusion
Trastuzumab - HER2 receptor in breast cancer
Cetuximab - EGFR receptor Colorectal/Head and Neck
Bevacuizumab - VEGF receptor Colorectal/Breast/Gynae
General rule for dental txs while on chemotherapy?
Avoid if not urgent
Urgent work completed before chemo
Do tx just before next cycle
If already on chemo:
- Find out length of cycle - 3 weekly/weekly/daily tablets
- In a 3 weekly cycle (most common) - max risk of immunosuppression is between 7-14 days
- Check FBC prior to urgent dental tx to ensure not neutropenic or low platelets
- Neutropenia neuts less than 1
- Thrombocytopenia - platelets less than 100
- Risk of bleeding if platelets less than 20/30
Why may an abscess be in an immunocompromised pt?
Can be source of infec for neutropenic sepsis - IV antibiotics and supportive measures provided
If no other source of infec or sepsis not improving = drainage of abscess and platelet transfusion if low with GCSF cover
Immunotherapy features?
PDL1 inhibitors - pembrolizumab
Immune checkpoints inhibitors - Nivolumab
Can cause an ‘itis’ in any organ (hepatitis, thyroiditis) that can be fatal
Can be effective in controlling cancers
Can provide a sustained benefit for months/yrs
When are bone txs used in cancer? Examples?
Used in adjuvant or palliative setting Either to reduce risk of SREs or decrease symptoms from SREs Bisphosphonates RANK ligand inhibitors Radium 223
What are bone metastases often a mixture of?
Osteoblastic and osteoclastic lesions
What are the clinical consequences of bone metastases?
Pathologic fractures
Radiotherapy to bone to prevent pain or fracture
Surgery to bone to prevent or stabilise fracture
Spinal cord compression = numbness/weakness, bowel incontinence and paralysis
Hypercalcaemia
Pain
What does metastatic bone disease do?
Increases bone resorption = osteoclast is key therapeutic agent
What occurs in bone destruction (bone metastases)
- Tumour cells produce factors that stimulate osteoblasts to secrete RANK ligand
- Osteoblasts increase expression of RANK ligand
- Overexpression of RANK ligand drives increased formation, func and survival of osteoclasts = excessive bone resorption
- Bone resorption releases growth factors from the bone matrix that may preserve tumour activity
Which are the most potent and least potent bisphosphonates?
Zoledronic acid = most potent
Etidronate = least potent
Metastatic bone disease tx and their goals?
RT - treat bone pain
Endocrine tx, chemo, tumour targeted therapies = anti-tumour
Orthopaedic intervention - repair bone
Analgesics
Bone targeted txs - bisphosponates, RANK ligand inhibitors, Radium 223 (inhibit bone cell function)
List examples of bisphosphonates
Zoledronic acid
Clodronate
Pamidronate
Ibandronate
Give an example of a RANK ligand inhibitor
Denosumab
How do bisphosphonates effect bone destruction?
Decrease activity of osteoclasts = Reduction in release of peptides - Slowed tumour cell growth - Reduced production of PTHrP - Decrease bone resorption
Pharmacokinetics of bisphosphonates?
Half life of circulating bisphosphonates - fast = 0.5-2hrs
50% of circulating bisphos is taken up by skeleton
Rate of uptake by bone is fast
Can remain in bone for 1-10yrs
Are liberated from skeleton during Oc resorption
What are the side effects of bisphosphonates?
Oral - upper gastrointestinal inflam, diarrhoea and abdominal pain
IV therapy
- Temporary fever and myalgia
- Electrolyte and mineral adverse events (severe hypocalcaemia, ca and vit D supplements needed)
- Renal toxicity rare at approved dose and schedule
Flu like symptoms after initial infusion
ONJ - mainly in pts with advanced malignancies and skeletal metastases
What is the prevalence of ONJ?
<1%
1% per yr on IV pamidronate/zoledronic acid
Related to potency and duration of tx
More common with IV formulas
ONJ risk management?
Reports primarily in pts with advanced malignancies and bone metastases
Minimise ONJ risk by;
- Dental exam before BP tx
- Avoid invasive dental procedures if possible during tx
- No date suggesting if discontinuation of BP decreases the risk of ONJ
In case of ONJ
- Reassess benefits/risk of continued BP tx
- Discuss options with pt
- Manage conservatively
- Healing can occur
How does denosumab work?
- Denosumab binds to RANK ligand = preventing activation of RANK receptor on osteoclasts
- = inhibition of Oc formation, func and survival
- = Prevention of maturation of osteoclasts, decreasing bone resorption and stopping the excessive bone destruction
Advantages of denosumab?
SC - more convenient than IV zoledronate
No concerns about renal safety = no renal monitoring required
Fever actue phase reactions
Negatives of denosumab?
Expensive
Hypocalcaemia - Rx Ca and vitamin D
Side effects - arm, leg, back pain, high cholesterol, muscle pain and bladder infecs
General rule for dental tx whilst on bisphosphonates/denosumab?
Pre-assessment before starting bisphosphonates or denosumab
Prevention is vital
While on bisphosphonates or denosumab:
- At the onset of symptoms: Suspend Rx until dental assessment to exclude suspicion of ONJ
- If not ONJ - restart 6 weeks after dental work
- If ONJ - suspend or stop (discuss risk/benefit with pt)
