Oncology Flashcards
What cancers is HPV associated with?
Cervical
Anal
Head and neck
What subtypes of HPV are cancerous?
HPV16 and HPV18
HPV16 produces E6 protein, which binds to and inactivates p53 protein leading to dysregulation of cell cycle and apoptotic pathways
What cancer is Epstein Barr Virus associated with?
non-Hodgkin’s lymphomas
What cancer is HTLV1 infection associated with?
T-cell lymphomas
What cancer is H. Pylori associated with?
MALT (mucosal associated lymphoid tissue) tumours
What is the 2nd commonest cancer?
Lung cancer
What are the different types of lung carcinoma?
- Small cell lung carcinoma
- Non-small cell lung carcinoma
a) Squamous cell
b) Adenocarcinoma
c) Large cell carcinoma
d) Adenocarcinoma in situ - Mesothelioma
- Sarcoma
- Lymphoma
What is the most common lung carcinoma?
Adenocarcinoma is now the most common lung cancer (40%) - it used to be squamous cell lung carcinoma until the 80s
What does small cell lung cancer arise from?
Endocrine cells called Kulchitsky cells
What type of lung cancer is more aggressive?
Small cell lung cancer
Grows rapidly and is highly malignant
70% are disseminated at presentation
Metastasise earlier in their course so often cannot be treated by surgery
What gene mutations are commonly found in adenocarcinomas?
EGFR - 19 & 21 mutations
ALK - translocation
ROS1 - mutation
Which patients is the EGFR mutation more common in?
East Asians
Females
Non-smokers
Young patients
What are the main causes of lung cancer?
Smoking - 90%
Occupation - asbestos exposure, uranium mining, ship building, petroleum refining
How does lung cancer usually present in order of most common symptoms?
Cough - 80%
Haemoptysis - 70%
Dyspnoea - 60%
Chest pain - 40%
Weight loss, anorexia, lethargy
Recurrent pneumonia
How does an apical Pancoast tumour present?
Horner’s syndrome
Ptosis, miosis, anhidrosis
Hoarseness of voice
How can a mediastinal tumour present?
Hoarseness of voice due to recurrent laryngral nerve palsy
SVC obstruction
What types of lung cancer can cause paraneoplastic syndromes?
Small cell lung cancer
Squamous cell lung cancer - hypercalcaemia
Large cell cancer - gynaecomastia
Give examples of paraneoplastic syndromes and their relevant hormone
Excess ACTH - Cushing’s
Excess PTH - hypercalcaemia
Excess HCG - gynaecomastia
Excess ADH - SIADH
What are some skin manifestations of lung cancer?
Dermatomyositis
Herpes zoster
Acanthosis nigricans
What signs might be seen on inspection of the hands in lung cancer?
Clubbing
Anaemia - pale palmar creases
Pain in the wrist - hypertrophic pulmonary osteoarthropathy
On auscultation of the chest, what sounds would be heard in lung cancer?
Monophonic wheeze due to partial airway obstruction
What factors of the history, examination and investigations would indicate squamous cell carcinoma?
Cigarette smoking
Hypercalcaemia - they secrete PTH-related peptide
Bronchial obstruction - often found centrally, close to bronchi
What factors of the history, examination and investigations would indicate adenocarcinoma?
History:
- Woman
- Non-smoker
- Asbestos exposure
Investigations:
- EGFR, ALK, ROS1 mutations
- Peripheral tumour
What might be seen on a chest x-ray in lung cancer?
Nodule Hilar enlargement Consolidation Pleural effusion Lung collapse Bony mets
If there is suspicion of lung cancer from a CXR, what following investigations should be carried out?
Sputum cytology
CT thorax for staging
Either:
- CT guided biopsy
- Navigation bronchoscopy if lesion cannot be reached by CT guided biopsy
PET scan to check for mets not seen on CT
Lung function tests to check suitability for lobectomy
What is the histopathology for small cell lung carcinoma?
Small blue oval-shaped cells
Absent nucleoli
Decreased cytoplasm
What is the TNM staging for lung cancer?
T1-4: tumour size and invasion
N1: same hemithorax as tumour
N2: nodes in mediastinum on same side as tumour
N3: lymph nodes on other side from tumour
M1a: mets to other lung; pleural/pericardial effusion
M1b: distant mets outside thorax
M1c: multiple mets in different organs
What is the mainstay treatment for small cell lung cancer?
Chemotherapy (SCLC is considered a systemic disease at diagnosis)
When is radiotherapy used in SCLC?
Adjuvant radiotherapy as primary treatment with chemo
Prophylactic cranial irradiation - brain mets are common so reducing those reduces risk of relapse
Palliative
What are the different options for treatment of non-small cell lung carcinoma?
Surgery – usually lobectomy but if severe consider bi-lobectomy/pneumonectomy
Radiotherapy – 3times/day for 12 days straight. 20% 5 year survival
Chemotherapy – neoadjuvant for radiotherapy or palliative
Immune therapy – 1st line alone or combined with chemo
What is the untreated life expectancy for SCLC? What does chemotherapy increase this to?
Untreated life expectancy = 2-4 months
Chemotherapy increases it to 12 months
What are the 2 main types of breast carcinoma?
Ductal carcinoma (85%) - epithelial lining of ducts
Lobular carcinoma (15%) - epithelium of terminal ducts of lobules
Which breast carcinoma is more infiltrative?
Lobular carcinoma - it can present similarly to gynaecological cancers
What genes are associated with increased risk of breast cancer and what chromosomes are they found on?
BRCA1 - Chr17
BRCA2 - Chr13
What risk factors associated with oestrogen exposure increase the risk of breast cancer?
Early menarche Late menopause HRT use Obesity (especially post-menopause) Nullparity First child after 30
Where is oestrogen produced?
Premenopausal women – oestrogen produced in ovaries
Postmenopausal women – synthesis in fat cells (adipose tissue), skin, liver, muscle, breast
What is the most common presentation of breast cancer?
Breast lump
Hard, painless lump with irregular margins
Fixed to skin/chest wall
What are other common presentations of breast cancer aside from breast lump?
Breast pain Skin changes - peau d'orange, skin dimpling Nipple discharge Nipple changes - paget's disease Axillary lymphadenopathy
What causes peau d’orange?
Oedema due to lymphatic invasion from tumour
What questions are important to ask in a breast cancer history?
- How long?
- Skin/nipple changes?
- Associated symptoms – discharge/pain?
- Related to menstrual cycle?
- Previous breast lumps?
- Lumps under arm?
- Family history
How do you investigate a suspected breast cancer?
Triple assessment
1) Examination - breast, axilla, supraclavicular fossa\
2) Radiology - mammogram, USS
3) Biopsy - fine needle aspiration, cytology, histology
What is the treatment of choice for localised disease in breast cancer?
Surgery
Either:
- Wide local excision to remove lump
- Mastectomy to remove breast
What is required in all breast cancer patients after conservative?
Adjuvant radiotherapy to residual breast tissue +/- lymph node areas
40 Grays in 15 fractions over 3 weeks
Reduces risk of local relapse by half
What determines the efficacy of endocrine therapy in breast cancer?
The presence of oestrogen and progesterone receptors (60%) because it blocks oestrogen action and production
What endocrine therapy is only useful in post-menopausal women?
Why?
Aromatase inhibitors (anastrozole, letrozole)
They stop oestrogen production by blocking the action of aromatase enzyme which converts cholesterol to oestrogen in fat cells
What are some side effects of aromatase inhibitors?
Mood changes Vaginal dryness Loss of libido Arthralgia Myalgia Decreased bone density
What endocrine therapy is only useful in pre-menopausal women?
Ovarian ablation
What endocrine therapy can be used in pre- and post-menopausal breast cancer patients?
Tamoxifen
Selective oestrogen receptor blocker
What is the risk with tamoxifen?
Endometrial cancer - warn patient about abnormal vaginal bleeding
What is HER-2?
What is its relation to breast cancer?
HER-2 is an endothelial factor receptor oncoprotein that allow rapid multiplication of the cell
15% breast cancers overexpress HER-2
What drug can be used in HER2 positive breast cancers?
Herceptin = transtazumab (monoclonal antibody)
Give for 12 months
What is a risk of herceptin?
Cardiotoxicity
i.e. it makes the heart baggy
It is reversible
Which breast cancers are most responsive to chemotherapy?
ER-negative
HER2-positive
What chemotherapy drugs are typically used in breast cancer?
EC (epirubicin + cyclophosphamide) for 3 cycles
Docetaxel for 3 cycles
(if no lymph nodes involved, only EC for 6 cycles)
What chemotherapy agents can be given for ER positive breast cancers?
CDK4/6 inhibitors
What are some poor prognostic indicators in breast cancer?
Triple negative HER2 positive High TNM stage Lymph node involvement >5cm mass Higher grade
What are 95% of prostate cancers?
Adenocarcinomas of glandular tissue in posterior/peripheral zone
Where do prostate carcinomas most common metastasise to?
Bone - especially spine
Lymph nodes
What genes increase risk of prostate cancer?
BRCA2
pTEN
What urinary symptoms might be seen in prostate cancer?
Decreased flow
Hesitancy
Frequency
Nocturia
Describe how the prostate feels on DRE in prostate cancer
Hard Enlarged Irregular/craggy Nodular Obliteration of median sulcus Immobile
What scale is used for grading of prostate cancer?
Gleason’s Pattern Scale
A pathologist looks at prostatic tissue under microscope and grades the morphology of the cells from 1 to 5
What investigation is done to diagnose prostate cancer?
Trans rectal ultrasound of prostate (TRUS) + biopsy - diagnostic
When should you avoid treatment in prostate cancer?
If it is asymptomatic
In patients where other conditions are more likely to kill
What surgery can be done for prostate cancer?
Robotic radical prostatectomy
What patients is surgery a better option for in prostate cancer?
Patients with localised disease and are symptomatic and have >10 year life expectancy
What risks are there with a prostatectomy?
Impotence
Urinary incontinence
What hormone therapies can be used in prostate cancer? (5)
1) Luteinising hormone release hormone (LHRH) aka GnRH agonists – interferes with release of gonadotrophins from pituitary so decreases testosterone -Need to cover initially with anti-androgen (cyproterone acetate) to prevent rise in testosterone
2) Gonadotrophin releasing hormone antagonist
3) Anti-androgens – compete with androgens at androgen-receptor
4) Oestrogen therapy
5) Bilateral orchidectomy (castration)
What are some side effects from hormone therapy in prostate cancer?
Impotence Loss of libido Tumour flare on initiation of treatment Loss of muscle Penis shrinkage
What chemotherapy is most commonly used in prostate cancer?
Docetaxel
When is hormone therapy used in prostate cancer?
Advanced metastatic disease
Neoadjuvant to surgery
Describe the pathophysiology of colorectal cancer
Normal epithelium > hyperproliferative epithelium > benign adenoma > severe dysplasia (pre-cancerous polyp) > adenocarcinoma > invasive cancer
What type of carcinoma are most colorectal cancers? What are some rarer types?
95% adenocarcinoma
Carcinoid
Gastrointestinal stromal tumour
Primary malignant lymphoma
What dietary factors increase risk of colorectal cancer?
Rich in animal fats + meat
Poor in fibre - less fibre prolongs transit time so colon is more exposed to carcinogens present in faeces (bile salts can be carcinogenic either directly or when degraded by bacteria present in faeces)
What genetic factors can increase risk of colorectal cancer?
HPNCC (a.k.a Lynch Syndrome)
FAP (familial adenomatous polypoposis)
Gardner’s syndrome
How does left sided colorectal cancer present?
Early change in bowel habit
Rectal bleeding with mucus
Tenesmus
Obstruction (left colon is narrower and doesn’t expand as easily)
How does right sided colorectal cancer present?
Weight loss
Iron deficiency anaemia
Abdominal pain
More advanced at presentation
What are the red flags for colorectal cancer?
Weight loss Blood in stools Change in bowel habit Abdominal pain Mucous in stools Anorexia
What is the screening programme for colorectal cancer?
- All 55+ are invited for one off flexible sigmoidoscopy
- All 60-74 year olds sent home test every 2 years
- Over 75s can ask for home test every 2 years
What investigations can be done for suspected colorectal cancer?
Colonoscopy + biopsy
CT colonography (combines CT scanning with insufflation of whole colon with gas, which can help identify synchronous polyps in bowel) – staging
What staging criteria is used for colorectal cancer?
Dukes Staging
A – confined to bowel wall B – invasion through bowel wall C – lymph node involvement C1 – apical/high tide node is clear C2 – apical node involvement D – widespread metastases
What treatment can be curative in colorectal cancer?
Radical resection
What treatment is not routinely used in colon cancer?
Radiotherapy due to risk of toxicity to adjacent organs
What therapy is used in medium risk rectal cancers?
Radiotherapy (adjuvant + neoadjuvant)
What therapy is used in high risk rectal cancers?
Chemotherapy (adjuvant + neoadjuvant)
What presentation defines neutropenic sepsis?
Neutrophil count < 0.5
AND EITHER
Single temp > 38.5 OR sustained temp > 38 for 1 hour
What microorganism are most neutropenic sepsis cases caused by?
Gram positive bacteria e.g. S. aureus, coagulase negative staph, alpha & beta haemolytic strep
What is the main risk factor for neutropenic sepsis?
Chemotherapy (especially within 6 weeks of receiving chemo)
What is the management for neutropenic sepsis?
BUFALO
Blood cultures Urine output - put catheter in Fluids Antibiotics - start broad spectrum within an hour of admission (piperacillin/tazobactam) Lactate Oxygen
What can you give to a patient with severe neutropenia (neutrophils < 0.1) and multi-organ failure?
Colony stimulating factors e.g. filgratim/lenograstim
They are haematopoietic growth factors that promote stem cell proliferation and shorten duration of neutropenia
What is the MASCC score?
Assesses risk of complications during febrile neutropenic episode
What cancers are spinal mets most commonly associated with?
Lung Prostate Breast Breast Myeloma Melanoma
What causes spinal cord compression?
Collapse or compression of vertebral body due to mets
OR
Direct extension of a tumour into vertebral column
How does spinal cord compression present?
Back pain (95%) exacerbated by movement, coughing and lying flat
Limb weakness
UMN/LMN signs depending on level of compression
How do you investigation a spinal cord compression?
Full spine MRI
Neurological examination
PR to assess sphincter tone
What is the acute management for spinal cord compression?
Dexamethasone 16mg + PPI (make sure to measure glucose)
MRI of spine
Refer to oncologists/neurosurgeons
What further management can be done in spinal cord compression?
Radiotherapy
Decompressive surgery (if there has been mechanical collapse of vertebra)
What is the prognosis of spinal cord compression?
If treated within 24 hours, 57% will be able to walk again
Patients with loss of motor function after >48h are unlikely to recover function
How does cauda equina syndrome present?
Back pain Radicular pain down legs Asymmetrical, atrophic, areflexic, flaccid paralysis of legs Saddle anaesthesia Decreased sphincter tone
What is the normal physiological process if there is high blood calcium level?
High calcium causes thyroid to release calcitonin
Calcitonin reduces absorption of calcium in kidneys
It also promotes osteoblasts to deposit calcium in bones
What is the normal physiological process if there is low blood calcium level?
Low calcium causes parathyroid gland to release PTH
PTH stimulates kidneys to absorb calcium
PTH causes kidneys to convert 25-hydroxy vitamin D to 1-25 dihydroxy vitamin D, which stimulates bowels to absorb calcium
PTH promotes osteoclasts to release calcium from bones
What is the most common cause of hypercalcaemia?
Primary Hyperparathyroidism
What cancers most commonly cause hypercalcaemia?
Non-small cell lung carcinoma Multiple myeloma Breast carcinoma Renal cell carcinoma Head + neck cancers
What blood results would indicate hypercalcaemia of malignancy rather than primary hyperparathyroidism?
Low albumin Low chloride Alkalosis Low potassium High phosphate High ALP
How do you manage hypercalcaemia?
- IV 0.9% saline 1L every 4 hours for 24h then every 6 hours for 48-72h
- Zolendronic acid 4mg IV or IV pamidronate
- Salmon calcitonin (S/C or IM) and corticosteroids (prednisolone PO)
What medication should you avoid in hypercalcaemia?
Thiazide diuretics
What can cause a high ALP with hypercalcaemia?
(higher bone turnover)
- Bone metastases
- Sarcoidosis
- Thyrotoxicosis
- Lithium
What most commonly causes superior vena cava obstruction?
Extensive lymphadenopathy in upper mediastinum from lung cancer or lymphoma
What are some possible benign causes of SVCO?
- Non-malignant tumours e.g. goitre
- Mediastinal fibrosis e.g. post-radiotherapy
- Infection e.g. TB
- Aortic aneurysm
- Thrombus associated with indwelling catheters
How does superior vena cava obstruction present?
Symptoms • Headache/feeling of fullness in head • Facial/upper limb oedema • Dyspnoea – worse on lying flat • Cough • Hoarse voice
Signs
• Oedematous face/neck
• Dilated veins in neck, chest, arms
• Stridor
How would brachiocephalic artery obstruction present?
Arm swelling
What is the management of SVCO?
Dexamethasone 16mg + PPI
Further options:
- vascular stenting
- radiotherapy
- chemotherapy
- LMWH (if thrombus confirmed)
What tumour markers are associated with germ cell/testicular cancers?
Alpha fetoprotein (aFP)
hCG
What benign conditions are relevant to aFP?
Liver cirrhosis
Pregnancy
Neural tube defects
What cancer is relevant to calcitonin?
Medullary thyroid
What cancer is relevant to CA-125?
Ovarian
What conditions is CA-125 low in?
Endometriosis
PID
What cancer is relevant to CA19-9?
Pancreatic
What use does measuring CA19-9 have in pancreatic cancer?
Monitoring the disease only
What tumour marker is associated with breast cancer?
CA15-3
What tumour marker is associated with colorectal cancer?
CEA
What else is CEA raised in?
Smoking
CKD
Chronic liver disease
IBD
What tumour marker is the most sensitive to the disease?
PSA in prostatic carcinoma
What cancer do raise immunoglobulins suggest?
Myeloma
What are tumour markers?
Substances produced either by, or in response to, tumour and are present in the blood or other tissue fluids and can be quantified
What other cancer is aFP raised in?
Hepatocellular cancer
What are UMN signs?
Hypertonia
Hyper-reflexia
Upgoing plantars
What type of scan is a PET scan?
Nuclear imaging that uses fluorodeoxyglucose (FDG) as a radiotracer
This allows a 3D image of metabolic activity to be generated using glucose uptake as a proxy marker
What is Pemberton’s sign?
Ask patient to raise their arms until they touch the side of their face
If they develop cyanosis, worsening of their shortness of breath or facial congestion, it is positive for venous congestion
How does ovarian cancer often present?
Non-specific abdominal symptoms
E.g.
- Bowel disturbance
- Abdominal distention and discomfort
What is the most common origin of bony mets?
In men: prostate
In women: breast
What cancer are women who have HNPCC at risk of other than colorectal cancer?
Endometrial cancer
What is Li-Fraumeni syndrome caused by?
Germline mutations to p53 tumour suppressor gene
What malignancies is Li-Fraumeni syndrome particularly associated with?
Sarcomas - it is diagnosed when an individual develops sarcoma under 45 years
Leukaemias
What kind of bone lesions are most common in prostate cancer and myeloma?
Prostate cancer - sclerotic bone lesions
Myeloma - lytic bone lesions
Therefore, myeloma often causes hypercalcaemia, whereas prostate cancer does not
What is the dose of radiation defined as in radiotherapy?
Irradiation absorbed by each kilogram of tissue expressed as Grays (Gy)
1 Gy = 1J/kg
Briefly summarise how radiotherapy works
X-Rays have very high energy and very short wavelength (they deliver energy through photons), which are produced by accelerating a stream of electrons and colliding them with a metal targets
The X-Rays are generated and delivered by a linear accelerator (LINAC)
High-energy photons produce secondary electrons in human tissue (whilst sparring the skin), causing DNA damage and leads to apoptotic or mitotic cell death
What is a fraction (in radiotherapy)?
One treatment session of radiotherapy
What is the most common method to deliver radiotherapy?
External beam radiation therapy
This can be:
- Image-guided radiotherapy = CT/MRI is used to target tumours while minimising radiation exposure of healthy tissues
- Stereotactic radiosurgery (e.g. gamma knife) = multiple radiation beams converge on the tumour e.g. brain tumours
What is the most common acute adverse effect of radioetherapy?
General fatigue - 80% patients
What is a common complication after head/neck irradiation, particularly if the parotids have been irradiated?
Loss of salivary flow leading to dry mouth
In radiotherapy, what does fractionating mean? What is the purpose of it?
A course of radiotherapy is spread over days or weeks.
Fractionating allows normal tissues to repair from the radiation damage, while tumour cells, which are less efficient to repair, do not recover
In radiotherapy, what is a beam of radiation called?
A field
Which tissues are most acutely damaged by radiotherapy?
Fast proliferating tissues
e. g.
- Skin
- Mucosa of GI tract
- Hair
- Bone marrow
Generally, what is the mechanism of action of chemotherapy?
Most agents target DNA either directly or indirectly
Therefore, chemo agents are preferentially toxic towards actively proliferating cells
How are chemotherapy doses calculated?
According to the patient’s body surface area
Most commonly used formula is DuBois formula
Carboplatin dose is calculated from renal function
Monoclonal antibody dose is calculated based on body weight
What acute/immediate complications can be experienced from chemotherapy agents?
Nausea/vomiting
Myelosuppression - neutropenia, anaemia, thrombocytopenia
Mucositis - aphthous ulcers, diarrhoea
Alopecia
Neuropathies - PNS (burning, tingling), ANS, CNS, ototoxicity
Acute arrhythmias
Transient rise of liver enzymes
Skin and soft tissue
- Palmar plantar erythema (hand-foot syndrome)
- Photosensitivity
- Nail changes - bow’s lines
What long term complications can be experienced from chemotherapy agents?
Infertility
Pulmonary fibrosis or pneumonitis
Secondary malignancies
Cardiac fibrosis
What is the screening programme for breast cancer?
Mammography
Ages 50-74yr every 3 years
What patients with NSCLC may be offered immunotherapy?
Those with high PDL1 expression
A molecule involved in controlling the normal immune response
What immuotherapy is offered to those with high PDL1 expression with NSCLC?
Pembrolizumab
What % of NSCLC are suitable for targeted therapy?
<10%
What investigations are done for prostate cancer?
PR PSA Isotope radionucleotide bone scan Urinalysis (haematuria) TRUS
When is a TRUS not performed in prostate cancer?
When clinical suspicion is high
eg PSA >100 with positive bone scan
What isotope bone can is performed in prostate cancer?
Radiolabelled technetium
Taken up by osteoblasts at sites of bone remodelling eg sclerotic bone mets in prostate cancer
Give two examples of LNRH agonist therapies used in prostate cancer
Leuprorelin
Goserelin
How are LNRH agonist therapies given in prostate cancer treatment
Monthly or 3 monthly
IM or SC depot injection
What are some side effects of NRH agonist therapies given in prostate cancer treatment?
Impotence
Loss of libido
Tumour flare
When does tumour flare occur in LNRH agonist therapy given in prostate cancer treatment? How is it avoided?
Occurs on initiation of treatment prior to the down-regulation of gonadotrophin
Avoided by short term concomitant anti-androgen therapy
What are some long term risks of LNRH agonists used for treating prostate cancer?
Cardiac risks
Osteoporosis
Give an example of a GnRH antagonist used in the treatment of prostate cancer
Goserelin
Leuprorelin
Triptorelin
How does oestrogen therapy work in prostate cancer?
Oestrogens inhibit LNRH production from hypothalamus
Why is oestrogen therapy rarely used in prostate cancer?
Side effects
Impotence, loss os libido, gynaecomastia, MI, stroke, PE
Give two examples of anti-androgen therapy used in the management of prostate cancer
Bicalutamide
Enzalutamide
What can enzalutamide be combined with in the treatment of prostate cancer?
GnRH agonists
What is the prognosis of prostate cancer?
Low risk = 99% 5yr survival
Metastatic disease = 3.5 yrs 5 median survival
What suggests a poor prognosis in prostate cancer?
Bone mets
Aggressive pathology
Younger age
What treatment is more suitable for elderly patients with prostatic carcinoma?
Radiotherapy
What are the 2 methods of radiotherapy for prostatic carcinoma and what are the pros/cons?
External beam radiotherapy (high energy Xrays from outside body) - risk of impotence and proctitis
Brachytherapy (radioactive seeds planted in prostate) - less risk of impotence and bladder problems
