Clinical oncology Flashcards
Cancer definition
Group of diseases characterised by uncontrolled growth and spread of abnormal cells within a body
Oncology/ oncologists
Specialism/ specialists in cancer
How many cancers?
Around 200
Classification of cancers
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
Prognostic makers to determine treatment pathways
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
How common is cancer?
1 in 3 lifetime risk
Increasing incidence for several types
Incidence of oral cavity cancer
Males higher than females
- males ~11/100,000
- females ~7/100,000
Risk factors for head and neck cancer
Smoking Alcohol Diet and nutrition Viruses -HPV -Epstein Barr Virus Immunosuppression Premalignant oral conditions -leukoplakia -lichen sclerosis Radiotherapy exposure
Risk factors for colorectal cancer
Dietary
Genetic
Risk factors for lung cancer
Smoking
Risk factors for breast cancer
Genetic
Obesity
Risk factors for skin cancer
Sun exposure
Risk factors for cervical cancer
HPV
Changes in incidence of oral cancer
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
Improved survival
Earlier diagnosis - > pt awareness (media, internet) -screening programs (colorectal, breast, prostate, ovary, cervix) Improved treatment -surgery -radiotherapy -chemotherapy
Treatment options
- Surgery
- Radiotherapy
- Chemotherapy
- Hormonal therapy
- Targeted therapies
- Immunotherapy
- Laser therapy
- Cryotherapy
- Best supportive care
- Any combination of these
Surgery
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
Side effects of surgery
Functional
Cosmetic
Risks of anaesthetic
Chemotherapy
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
Different mechanisms of action of chemotherapy
Platinum -cisplatin/ carboplatin/ oxaliplatin Taxanes -docetaxel/ paclitaxel Anti metabolites -5 fluorouracil/ methotrexate Alkylating agents -dacarbazine/ temozolamide Anthracyclines -doxorubicin/ epirubicin
Chemotherapy adjuvant treatment
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
Chemotherapy -palliative treatment
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
Chemo side effects
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
More modern targeted agents
Tyrosine kinase inhibitors (oral) -Vermurafenib (BRAF mutation melanoma) -Gefinitinib -Imatinib -Sunitinib Monoclonal antibodies (IV infusion) -Trastuzumab (HER2 receptor breast cancer) -Cetuximab -bevacuizumab
Radiotherapy
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
Radiotherapy
-therapeutic vs diagnostic
Energy of photos higher in therapeutic setting as opposed to diagnostic setting
- diagnostic x-rays up to 150KV
- therapeutic photons 80KV to 20MV
How does radiotherapy work?
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
Side effects of radiotherapy
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
Intention of radiotherapy
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
Dose and number of radiotherapy treatments (fractions) depends on
Area being treated
Intention of treatment - curative vs palliative
Curative radiotherapy
Complex planning Accurate localisation - CT Longer course More early side effects Less late side effects
Palliative radiotherapy
Simple planning Simple localisation - X-ray Short course Less early side effects More late side effects
Radiotherapy treatment modalities
X-rays -superficial radiotherapy -megavoltage radiotherapy 6-20MV Electron treatment 6-20MeV Bracytherapy: insertion of isotopes into tumour
Superficial radiotherapy
100KV photons
Treats to depth of 6mm
Good for superficial BCC and SCC
Megavoltage x-rays and e- treatment
The linear accelerator
CT planned radiotherapy
Less dose to underlying structures
Less toxicity?
Stereotactic radiosurgery
Brain metastasis
- <3 lesions of 3cm size
Single treatment of high dose
Types of head and neck cancer
Oral cavity -floor of mouth -anterior 2/3 tongue -alveolus -retromolar trigone -hard palate Nasopharynx Oropharynx Larynx -supraglottis/ glottis/ post cricoid Hypopharynx Sinuses
Pathology of head and neck cancer
Squamous cell cancer 90% (arising from mucosa) Adenocarcinoma Small cell carcinoma Sarcoma Lymphoma Skin -SCC -BCC -malignant melanoma -merkel cell tumour
Demographics of head and neck cancer
Males > females 2:1
Peak incidence 60-75 years
Mortality: 3000 deaths/ year in England and Wales
Human Papilloma Virus
DNA virus
72 L1 capsid proteins
Orogenital transmission
Cervical and oropharyngeal SCC type 16 most common
HPV in head and neck cancer
+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
Patterns of spread
Locally -soft tissues -cartilage -bone -nerves Lymph nodes -very common esp. nasopharynx and oropharynx Vascular -to lungs, bone and liver occurs late
How is the decision made about treatment for an individual pt and their cancer?
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
Decision making
Should happen in joint clinic
- surgeon
- oncologist
- specialist nurse
- plastic surgeon
- speech and language therapist
- dietician
- (psycology input)
Investigations needed:
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)
Other investigations
Bone scan
CT/ MRI scan of brain
Angiograms
etc
General management principles of early stage disease
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
General management principles of locally advanced disease
Surgery followed by Chemoradiotherapy
Chemoradiotherapy alone
Induction Chemotherapy followed by Chemoradiotherapy
General management principles of metastatic disease
Palliative Radiotherapy
Palliative Chemotherapy
Best supportive care
Non-surgical oncology for H&N cancer
Radiotherapy
Chemotherapy
Targeted therapy
-organ preservation: primary treatment
-used alongside surgery to > chance of cure (adjuvant treatment)
-often combined together: multimodality therapy
Head and neck radiotherapy
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
Verification process (radiotherapy)
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
Early side effects of head and neck radiotherapy
Xerostomia Altered/loss of taste Mucositis Loss of hair Fatigue Cough Soreness of skin -dry desquamation -moist desquamation
Late side effects of head and neck radiotherapy
Xerostomia Altered taste Osteo-radionecrosis Alopecia Hypothyroidism Sub-cutaneous fibrosis Second malignancy Altered pigmentation
Effects of radiotherapy on oral cavity
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
Radiotherapy technology
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)
Chemotherapy in head and neck cancer
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
Early side effects of chemotherapy
Alopecia Bone marrow toxicity -neutropenia -thrombocytopenia -anaemia Mucositis Diarrhoea Nausea/vomiting Peripheral Neuropathy Ototoxicity Altered taste
Late effects of chemotherapy
Infertility Early menopause Pulmonary fibrosis Renal impairment Cardiomyopathy Infertility Peripheral neuropathy Second malignancy
Dentists and oncology
Diagnosis of oral cavity tumours Health promotion Dental assessment pre-treatment -RT, chemotherapy, bisphosphonates Pts receiving chemo may require dental work -abscess -beware neutropenia & thrombocytopenia -may need to ask oncologists opinion Post treatment follow up Screening for oral cancer Maxillo-facial surgeons Restorative dentists
General rule for dental treatments while on chemotherapy
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
Timing for dental work while on chemo
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
Dental abscess in immunocompromised pt
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
Dental work for pts on targeted treatments
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
Immunotherapy
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
Bone treatments in cancer
Can be used in adjuvant or palliative setting
Either to < risk of SREs or < symptoms from SREs
Bisphosphonates
RANK ligand inhibitors
Radium 223
Metastatic bone disease
> 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)
- **
Pharmacokinetic properties of bisphonsphonates
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
Side effects of bisphosphonates
Oral therapy
- upper GI inflammation
- diarrhoea and abdo pain
Safety profile of IV bisphosphonates
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)
ONJ
<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
What do we know about ONJ and risk management?
Spontaneous reports primarily in pts with advanced cancer and bone mets
- freq. estimates vary but <1%
- etiology and pathogenesis poorly understood
Recommendations for minimising ONJ risk
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
In case of ONJ
Reassess benefit/ risk of continued BP therapy
Discuss options with pts
Manage conservatively
Note that healing of lesions has been reported in most cases
General rule for dental treatments of pts on bisphosphonates
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)
Denosumab advantages
Given SC, more convenient than IV Zoledronate
No concerns about renal safety, so no renal monitoring required
Fewer acute-phase reactions
ONJ zoledronic acid vs denosumab
Similar BUT Denosumab expensive
Denosumab side effects
Back pain Arm and leg pain High cholesterol Muscle pain Bladder infection Hypocalcaemia - prescribe calcium and vit D
