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Flashcards in Oncology Deck (174)
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1

What's the difference between tumour grade and stage? (2)

Grade: how the cells look / level of differentiation (NEED HISTOLOGY)
Stage: how big it is/ how spread it is (TNM) (NEED CT)

2

uses of tumour markers? (5)

- screening
- diagnosis
- prognosis
- response (to treatment e.g. PSA)
- relapse/ surveillance

3

HCG indicates what? (4)

- gestational trophoblastic disease (hyatiform mole, choriocarcinoma)
- non-seminomatous testicular cancer
- seminoma
- pregnancy

4

PSA indicates..? (5)
uses in prostate cancer (3)

- prostate problems: cancer, BPH, rectal exam, prostatitis
- UTI

- monitoring response to treatment
- surveillance
- can request it at GP for identifying potential cancer but poor sensitivity so not used in screening!

5

CEA used in which cancer monitoring? (1)
what else can CEA indicate? (6)

- cell surface antigen elevated in a range of cancers, commonly colorectal
(degree of elevation linked to the stage)

also elevated in
- smoking
- IBD
- hepatitis
- pancreatitis
- gastritis

6

CA-125 indicates which cancers? (5)
what non-cancerous conditions (5)

- 82% ovarian cancer
- pancreatic (65%)/ lung (32%)/ colorectal (21%)/ breast (12%) cancer
(also perioteoneal,endometrial and fallopian tube cancers but obviously rarer: remember Georgia finding perioteonal cancer in GP with CA-125)

- 6% benign (pregnancy, mensuration, normal, fibroids, PID, liver disease)

7

where is aFP made? (3)
what does it indicate if riased? (3)
what do higher levels mean...? (1)

- foetal yolk salk
- liver
- instestines

- hepatocellular carcinoma
- hepatitis
- teratoma

Teratoma= most common ovarian germ cell tumour (benign) aka dermoid cyst
They are most common in women during their reproductive years (from teens to forties).

high levels --> poor prognosis

8

Response assessment of tumours in imaging:
what are the levels of tumour response? (4)

Complete response: no disease detectable

Partial response: all lesions shunk by >30% (but still present)

Stable disease: <30% shrunk OR <20% increase

Progressive disease: >20% increase in size OR new lesions

9

risk factors to consider cancer? (12)

- age
- sex
- FHx
- smoking
- alcohol
- diet
- ethnicity
- drug use
- PMHx
- environmental exposures
- weight
- occupation
probably more!

10

What is final cancer sub-type confimed by? (1)

cancers confirmed HISTOLOGICALLY
- needed to diagnose cancer sub-types / prognosis

11

Side effects of radiotherapy:
acute (3)
long-term (5)
other (1)
when do the side-effects usually occur in acute and chronic? (2)
are they reversible? (2)
how is long-term effects managed? (1)

acute: (generally reversible) -ITIS/ inflammation
- diarrohea
- oral mucositis
- localised skin reaction
(depends where it is done!)

long-term: (generally irreversible) -OSIS /scarring
- fibrosis
- blood vessel damage
- INFERTILITY
- skin atrophy
- risk of second malignancy

- teratogenic!!!!!!

ACUTE:
- usually after first 5-10 fractions
-side effects tend to increase during treatment and hit peak in first few weeks following the end of treatment --> if they're bad at the end of the treatment they'll likely get WORSE over next couple weeks
- generally reversible
(as normal cells eventually repair themselves once treatment is finished)

LATE:
- > 3 months after, sometimes years later
- often irreversible and worsen over time
- many need MDT management

12

what is adjuvant and neo-adjuvant therapy? (2)

neoadjuvant is BEFORE the primary cancer treatment

adjuvant is AFTER the primary cancer treatment

13

Uses of radiotherapy in cancer? (3)
what are the types of radiotherapy? (4)
most common? (1)

- curative/ radical/ definitive/ primary treatment
- neoadjuvant/ adjuvant to surgery
- palliative setting (reduce side-effects of cancer)
part of the management of 40% of all patients cured

- using photons/x-rays
- electrons
- radio-isotopes
- protons

External beam radiotherapy using photons/x-rays is the most common form of radiotherapy used in the UK.

14

Toxicity of radiotherapy is dependant on:
treatment factors (4), co-morbidities (3) other (4)

- total dose
- total volume treated
- dose per fraction
- overall treatment time

- diabetes
- IBD
- smoking

- intrinistc radio-sensitivity of the cancer cells
- tumour hypoxia
- tumour repopulation
- additional treatment

15

Steps in radiotherapy pathway (10)
dose measured in..? (1)

1 diagnosis
2 MDT
3 immobilization
4 planning CT scan
5 disease delineation by oncologist
6 additional margins added
7 complex treatment plans developed
8 daily treatments and monitoring
9 clinical review during treatment
10 long term follow up

The patient needs to be in a consistent position for both the CT scan and during the delivery of radiotherapy and may require immobilisation such as with a Perspex mask for head and neck cancer patients

- dose expressed in Gray (Gy)

16

Defintion of GTV (1), CTV (1) and PTV (1)?
What else is highlighted on the scans? (1)

Gross tumour volume
(the tumour)

Clinical target volume
(added margins to allow for microscopic disease spread)

Planning target volume
(added margins for daily variations in patient and tumour position e.g. breathing)

"organs at risk" are also highlighted on the radiographs

MLC stands for multi-leaf collimator which is part of the head of the radiotherapy machine and helps to shape the beam of radiation.

17

Brachytherapy:
what is it? (1)
two main types? (2)
benefits?
which are the commonest cancers for it used in? (4)
what is important to inform the patient of in brachytherapy? (1)

where radiation sources are placed within or close to the tumour --> high-dose radiation to small tumour volume

- intracavity: placed in cavity e.g. uterus/ cervix
- interstitial: put into the target e.g. prostate

- low radiation dose to normal tissue

- prostate
- gynae
- oescophageal
- head and neck

- radiation protection is important!! the patients are radioactive!!!

18

forms of systemic anti-cancer therapy (5)

- cytotoxic chemotherapy
- hormone therapy
- biological therapy
- immmunotherapy
- radioactive isotopes e.g. iodine

19

aims of chemotherapy (4)

- primary treatment
- destroy remaining cells AFTER surgery/radiotherapy (adjuvant)
- shrink cancer BEFORE surgery (neo-adjuvant)
- palliative

20

meaning of:
radical (1)
primary (1)
neo-adjuvant (1)
adjuvant (1)
chemoradiation (1)
palliative (1)
**high-dose chemotherapy** (1)

- curative intent
- alone for cure
- before
- after
-with raidiotherapy
- incurable disease
- intensive drug treatment to kill cancer cells, but that also destroys bone marrow and can cause other severe side effects --> followed by bone marrow or stem cell transplantation to rebuild the bone marrow

21

what is a chemotherapy course? (1)
how long are they usually? (1)

the planned number of cycles
(most are ~6 months long before toxicity is too high)

22

in chemotherapy, why do you...
- administer drug combinations? (3)
- schedule treatment in cycles? (2)
- administer optimal dose (1)
- when would you give high-dose chemotherapy? (1)
- which cells affected by chemo most? (2)
- what are the two main side effects because of this? (2)

- different actions --> KILL MORE cells
- decrease chance of RESISTANCE
- different SITES of toxicity (dose maintained for each drug)

- allows normal cells to recover
- increases tumour clearance

- ensure effective but tolerable side effects

- use high-dose if long term survival or cure are possible (as damages bone marrow and --> transplant)

- haematopoietic stem cells
- lining of GI tract
---> myelosuppression (low blood counts) and mucositis

23

main principles of chemoterapy? (5)
how are doses calculated? (2)

- administer drugs in combinations
- schedule in cycles
- administer optimal dose
- use maintenance only where evidence supports it
- use more effective route (IV, oral, systemic, regional (intravesical, intraperitoneal, intraarterial))

calculate doses according to:
- body surface area
- renal function

24

'late' complications of chemotherapy? (6)

- second malignancy
- fertility: store sperm/ fertilised ova/ cryopreservation of sections of ovary
- pulmonary fibrosis or pneumonitis
- cardiac fibrosis: younger pts. more susceptible, dose-dependent + predictable
- psychological (PTSD, depression, financial, insurance, social isolation, strained relationships, education/employment difficulties)
- social

25

'immediate' chemotherapy effects on:
- GI (3)
- neuro (3)
- urinary (2)
- cardiac (2)
- hepatic (1)
- skin (4)
- other (4)

- nausea/vomitting
- diarrhoea (colitis/ small bowel mucosal inflammation)
- constipation (dehydration due to nausea+decreased water intake)
- oral mucositis

- peripheral neuropathy
- autonomic neuropathy
- ototoxicity

- nephrotoxicity
- bladder toxicity

- arrythmia
- ischaemia

- rise in liver enzymes
- rarely fulminant hepatic failure

- extravasation
- palmar plantar erythema; red hands (think of podcast where he couldn't play cricket with his sons)
- photosensitivity
- pigmentation (black hands/ finger nails)

- myalgia and arthralgia (paclitaxel- use NSAIDS)
- allergic reactions
- lethargy
- alopecia (regrows after chemo stopped)
- myelosuppression (bone marrow supplression)
- lethargy + general malaise
- allergic reactions (paclitaxel and docetaxel)

most return to normal after a while

26

Nausea and vomitting management:
what to give before chemo? (2)
going home from chemo? (2)
anticipatory nausea? (1)
why is N&V monitoring so important in chemo? (1)

- ondeansetron
- dexamethason

- metroclopramide
- dextramethasone

- lorazepam

Steroids and benzodiazepines often given concurrent to other antiemetics as have some antiemetic effects themselves but also increase effectiveness of the antiemetic

- important to control N&V from the outset with chemotherapy to maximise compliance
- PRN antiemetics are less effective than just giving it prophylactically

27

Four main oncological emergancies? (4)

- neutropenic sepsis
- metastatic spinal cord compression
- hypercalcaemia
- SVC obstruction

28

Definition of neutropenic sepsis (2)

- absolute neutrophil count <1*10^9/L
AND

- single temp >38.5oC
OR
- sustained temp >38oC for 1 hour

NB: normal temperature is 36.5–37.5 °C

29

What do you want to ask about in neutropenic sepsis histories? (4)

1- chemo drugs
+ what drug? ~some are more prone to neutropenic sepsis
+ how is it take? oral/PIC line ~source of infection!
+ how long have they taken it? within 3 weeks of chemotherapy, you can get neutropenic sepsis

2- previous episodes

3- localizing symptoms
+ try to find source: ask rash/ PIC line/ cough/ recent urination

4- allergies

remember neutorpenic sepsis is just fever + neutropenia ---> can happen if immunocomprimised/ on immunosuppressants, doesn't have to be chemo

30

common pathogens neuropenic sepsis
- gram +ve (3)
- gram -ve (3)
- fungi (2)

- S. aureus
- coagulase -ve staph
- alpha and beta haemolytic strep

- E. coli
- klebsiella
- pseudomonas

- candida
- aspergillosis

31

Assessment of neutropenic sepsis? (1)
managment neutropenic sepsis? (6)
time frame? (1)

- ABC

- BUFALOS

B- blood culture from ALL lines + swab anything wet (sputum, urine, stools, wounds)
- atypical pneumonia screen?
- CXR if indicated
- also take FBC, U&E, LFT, glucose, venous gas, clotting, group&save
- write sepsis on request form

U- urine monitoring
- hourly monitoring
- catheterize unless contraindicated

F- fluid resucitation
- If BP systolic <90 mmHg or lactate >4 mmol/L give up to 30 mL/kg of Hartmann’s and reassess (in 250-500 ml boluses, assessing response each time)

A- Abx
- refer to trust antimicrobial guidelines (Puperaxilllin/ tazobactam) + CHECK ALLERGY STATUS
- discuss microbiology

L- lactate
>2mmol/L=sepsis

O- O2

S- Senior review ST3 or above within the hour

within 1 hour!

ideally take blood cultures before starting ABx, but just do it off the same cannula

32

what scores neutropenic sepsis severity? (1)
how does this score affect managment? (1)

MASCC score
(Multinational Association of Supportive Care in Cancer)
- low score means patients can be treated as outpatient with early switch to oral antibiotics

MASCC score includes symptoms, hypotension, COPD, age, etc

NB: all admitted straight away, MASCC just tells you which can be switched to oral earlier

33

.

.

34

how common is metastatic cord compression of cancer? (1)
main cancers that cause it? (4)
presentation below and above L1? (2)
what to do?? (2)

COMMONEST neurological complication of cancer
- occurs in 5% of all cancers

breast
prostate
lung
haematological
(same 4 as the hypercalcaemia!)

66% of metastatic secondaries to bone arise from breast or prostate

- below L1= UMN
- above L1= cauda equina
60% of patients have pain

- URGENT MRI of WHOLE spine
- Inform Clinical Oncology SPR on call! same as other emergencies.. you want the consultant oncologist to know about this!

35

presentation metastatic spinal chord compression (4)
other red flag signs of back pain? (6)

- back pain
- leg weakness
- sensory loss/ saddle anaesthesia
- loss of control of bladder/bowels: urinary retention and/or loss of anal tone

- age: <20 or >55
- trauma
- weight loss associated
- pyrexia
- thoracic back pain
- constant pain at night and at rest

36

management metastatic spinal chord compression (5)
in which patients do you perform surgery? (4)
time frame? (1)

- lay flat
- dextramethasone16mg + PPI cover IMMEDIATELY (whilst awaiting investigations..)
- urgent MRI of WHOLE SPINE within 24hr
- consider neurosurgical intervention
- radiotherapy
--> rehabilitation

surgery if:
- single area
- good performance status
- predicted survival greater than 3 months
- not paraplegic for more than 48 hours

investigate early as you want to treat them within 48 hours
surgery has long recovery time - make sure recovery is worth the prognosis

- side effects of radio: pain flare, nausea, sickness, diarrhoea, tiredness

37

superior vena cava obstruction: main cancer that causes it? (1) other causes: malignant? (6) benign (5)

1. LUNG CANCER; most commonly NSCLC but in relativeterms more common in SCLC
2. Non-Hodgkins lymphoma (mediastinal lymph nodes - widened on CXR)

there are both benign and malignant causes:
- oesophageal
- lymphoma
- mediastinal lymphadenopathy
- germ cell tumours
- thymoma
- tumour associated thrombus

- non malignant tumours e.g goitre
- TB
- mediastinal fibrosis (idiopathic, post-radiotherapy)
- aortic aneurysm
- thrombosis

(think about whats in that area)

38

presentation superior vena cava obstruction? (6)

- breathless
- headache worse on coughing
- facial/ neck/ arm swelling
- distended neck and chest veins
- cyanosis
- visual disturbance

39

investigations superior vena cava obstruction: imaging (2)
what do you do after that? (1)
what might they decide to do? (3)

- CXR
- CT thorax

- give dex/PPI and call an oncologist

- tumour markers
- bronchoscopy (and biopsy if first presentation)
- mediastinoscopy

40

management superior vena cava obstruction for all (1) and depending on cause (4)

- dextramethason 16mg (+PPI cover)

depends on cause:
- vascular stenting (using radiological guidance) - normally everyone
- chemotherapy
- radiotherapy
- LMWH -> if thrombus

lots of SVCO tumours very receptive to chemo as fast growing (and chemo targets rapidly dividing cells)

41

what is spinal cord compression caused by? (6)

pressure on the spine due to:
- cancer

- osteoarthritis
- RA
- spinal injury
- infection
- scoliosis

42

main principle of hypercalcaemia (1)

imbalance between bone resorption and calcium excretion

43

treatment hypercalcaemia? (4)

- saline !!!!!!!!!! 1L/4hr for 24 hrs, 1L/6hr for 48-72hrs

- consider furosemide
(loopdiuretic that forces diuresis and promotes Ca excretion)

- bisphosphontes (+ monitor renal fucntion)
(inhibits osteoclastic bone resoption, IV pamidronate or zolindronic acid)

- calcitonin and corticosteroids
(SC/IM salmon calcitonin with oral prednisolone)


if Ca2+ >3.0 or symptomatic --> at least 3L of sodium chloride in 24 hours, stop thiazide diuretics, consider furosemide

44

symptoms hypercalcaemia (lots)!! (7 categories)

Stones

Bones:
- pain

Groans:
- lethargy/ fatigue
- weakness

Moans:
- nausea
- vomitting
- abdo pain
- weight loss

Thrones:
- polyuria
- polydipsia + dehydration

Pscyhiatric overtones:
- confusion
- proximal neuropathy
- seizure
- coma
- anxitey/ irritability
- halluciantions

+ CARDIAC
“Stones, Bones, Groans, Moans, Thrones, and Psychiatric Overtones!”+ cardiac

45

cardiac symptoms hypercalcamia (7)

- bradycardia
- short QT
- wide T waves
- prolonged PR
- BBB
- arrythmia
- arrest

46

Most common cancers in women (3) and men (3)

- breast
- lung
- bowel

- prostate
- lung
- bowel

47

how common is breast cancer? (1)

1 in every 12

48

risk factors breast cancer non-modifiable (9) and modifiable (6)

- age
- women
- oestrogen exposure (+reproductive history)
- PMH
- FH (+genetic mutations: BRCA1 and BRCA2)
- dense breasts
- ionising radiation/ radiotherapy

- exercise
- weight
- taking hormones
- reproductive history
- alcohol
- research also suggests smoking, chemical and night shift work

49

What non-modifiable (9) and modifiable (6) reproductive factors contribute to breast cancer?

- early mensural periods (55yrs
(i.e. anything with more hormones)

- first child after age 30
- not breastfeeding
- not having a full-term pregnancy
(again, think anything that increases number of periods)

50

symptoms which can indicate breast cancer (5)

- nipple discharge
- nipple inversion
- inflammation/skin changes
- mass on breast or regional lymphadenopahthy
- metastatic disease symptoms

51

2 week referral breast cancer? (2)
when to consider referral but not necessarily go for 2-week? (3)

- 30+ and unexplained breast lump
- 50+, unilateral nipple discharge, retraction, or other unexplained nipple signs

- skin changes
- lump in axilla
- under 30, unexplained breast lump (consider non-urgent referral)

52

breast cancer screening age (1) and frequency (1)?

50-71st birthday (earlier if v high risk)

every 3 years

53

ways to offer support someone through breast cancer (4)

- assign a named breast cancer nurse specialist
- prompt access to pscyhological support
- inform about risk of lymphedema (provide info)
- offer information on early menopause (may be caused due to treatment)

54

How is breast cancer diagnosed? (3)

triple assessment
- clinical
- mammography/ USS
- core biopsy/ FNA

55

TNM staging: T(5) N(4) M(2)
DON'T LEARN

T0- no primary tumour
Tis- in situ disease
T1- invasive tumour 2cm
T2- tumour 2-5cm
T3- primary tumour>5cm
T4- skin involvement

N0- no regional lymph node involvement
N1- mobile axillary nodes
N2- fixed axillary nodes
N3- internal mammary nodes

M0- no metastasis
M1- distant metastasis


varies for other cancers e.g. prostate

56

treatments for breast cancer (4) which is the aims of each/when are they done? (2)

SURGERY
initial treatment for localized disease= mastectomy

CHEMO
-adjuvant
- or palliative

RADIO
- conservative surgery (all patients require radio to residual breast tissue)
- palliative

ENDOCRINE THERAPY
- adjuvant

57

endocrine/hormone therapies in breast cancer (4)

- tamoxifen (ER positive)

- herceptin (HER2 positive)

- aromatase inhibitors

- ovarian ablation

58

5 year survival breast cancer percentages?

stage 1- 84%
stage 2- 71%
stage 3- 48%
stage 4- 18%
don't learn

59

what % of people get cancer?
what % die from it?

most common types? (4)

- 1/3 will get cancer at some point in their lives

- 1/4 will die from it

--> major PUBLIC HEALTH problem

- breast
- lung
- prostate
- GI
(each with many subtypes)

60

In what ways can public health measures impact cancer prevalence? (5)

reduce risk factors within the population:
- smoking
- diet
- exercise
- sunburn
- radiation protection

61

what is the common etiology of
- Burkitt's lymphoma? (1)
- leukaemia? (1)

- Epstein Barr virus (EBV)

- radiation

for many cancers a combination of several agents may be necessary, allowing the accumulation of genetic aberrations that leads to a malignant phenotype

62

what are the classes of aetiological agents of cancer? (6)

- inherited conditions (specific gene defect e.g. BRCA1)
- chemicals
- physical (radiation)
- diet
- drugs
- infective
- immune deficiencies (evidence people with HIV/ immunosuppresed are at increased risk of tumours - possibly the immune system is involved in tumour surveillance?)

63

examples of inherited cancers? (4)

- neurofibromatosis
- adenomatous polyposis coli
- familial breast cancer (e.g. mutations in the tumour suppressor genes breast cancer susceptibility gene 1 (BRCA1) and BRCA2)
- von-Hippel Lindau syndrome
- Li-Fraumeni syndrome (p53 is important in almost all cancers)

64

what is the mechanism by which chemicals cause cancers? (1)
examples of chemicals (5) and what type of cancers they lead to (5)?

damaging cellular DNA and inducing mutations in oncogenes and tumour suppressor genes

- cigarette smoke (causes mutation in p53 tumour suppressor gene)
- aromatic amines (a/w bladder cancer)
- benzene (leukaemia)
- wood dust (nasal adenocarcinoma)
- vinyl chloride (angiosarcoma)

65

describe what a 'physical' carcinogen is? (1)

what is level of risk associated with? (2)

DNA damage due to radiation accumulation in tumour-suppressor genes and oncogenes
can be UV, radiation, chronic inflammation

- radiation source
- level of exposure

accumulation of radioactive isotope in a particular tissue may --> tumour e.g. thyroid cancer and radioactive iodine.

66

how can low fibre diets lead to cancer if you ingest a carcinogenic food (e.g. nitrosamines)?

increased transit time through the bowel - thereby increasing exposure to carcinogenic substances

67

name the infective agents which are associated with cancer (5) which cancers are they commonly associated with?

- HPV: cervical and anal cancers

- EBV: non-Hodgkin's lymphoma (NHL) and other lymphomas

- HBV (Hep B): 100* risk of hepatocellular

- retrovirus: integration into the cellular genome retroviruses can cause abnormal overexpression of oncogenes --> HTLV1 a/w T-cell lymphomas

- H. Pylori: a/w mucosal associated lymphoid tissue (MALT) tumours


In HPV: The E6 protein produced by HPV16 binds to and inactivates the p53 protein. This leads to dysregulation of the cell cycle and apoptotic pathways and subsequent malignant transformation of epithelial cells infected.

68

What is the purpose of staging and grading? (2)

- indicate prognosis
- offer appropriate treatment choice

i.e. if in lymph nodes, risk of metastasis is high and adjuvant chemotherapy may be offered aswell.

69

what forms of radiology may be use to guide cancer biopsies? (2)

- CT
- US
under local anesthesia

70

uses of PET-CT scan (2)

- supplements CT scan to detect areas of intense metabolic activity --> can detect areas of tumour spread which may be missed by CT alone

used routinely now in cancers such as esophagus and lung

71

what imaging is used for staging? (2)

- CT
CHEST and ABDOMEN

- MRI
BONE and SOFT TISSUE and
regions where bone causes artefact in the CT appearances such as the PELVIS or the POSTERIOR FOSSA of the brain.
(gold standard for imaging neurospinal, rectal, prostate and musculoskeletal tumours, and is used for staging some subtypes of head and neck cancer)

(although remember histology required to make accurate diagnosis)

72

when would you use imaging in cancer follow-up? (1)

- when detection of asymptomatic relapse has been shown to affect clinical outcome further use of radiology for surveillance is justified (e.g. testicular tumours)
- in most cancers routine follow-up imaging is of no proven benefit

NB: Don't request things that won't change management!

73

In CT scanning, why would you give:
- IV contrast medium? (1)
- oral contrast medium? (1)

- which patients would you NOT give this too? (1)
- which patients are you concerned about CT scans in general? (2)

- to delineate vascular structures and to demonstrate tumour enhancement (thus increasing lesion detection, particularly in the liver)
- outline GI tract, demonstrate intra-luminal pathology or bowel obstruction and avoid misinterpretation of bowel loops as mass lesions

- RENAL IMPAIRED patients as contrast can be nephrotoxic

CT caution in:
- pregnancy/ women of child-bearing age
- anyone exposed to lots of radiation

74

what imaging is used for serial measurement of lesions (response assessment) (2)
which is not appropriate? (1) why? (2)

CT or MRI

NOT ultrasound
- operator dependent
- less reliable for the serial measurement of lesions for response

75

What are the two main properties you want in tumour markers for diagnosis? (2)
how can these values be altered? (1)

- sensitiVity
(true positiVes)
out of positives diagnosed out of all ACTUAL positives (TP+FN)

- specificity
(true negatives)
out of all ACTUAL negatives

the specificity of any test can increase if the cutoff value is moved. For example, αFP levels greater than 500 ng/ml are rarely seen except in patients with hepatocellular carcinoma or germ cell tumours of ovary or testis

76

classes of tumour markers (6)

- cell-surface glycoproteins (e.g. CA125, CEA, CA19.9)

- oncofetal proteins (HCG, aFP)

- enzymes (Alkaline phosphatase, lactate dehydrogenase etc)

- hormones (ADH, thyroglobulin)

- immunoglobulins (light chains)

- nucleic acids (mutations in DNA)

don't bother learning

77

problem with using tumour markers for screening:
false positives (4)
false negatives (2)

- false positives can cause anxiety
- inappropriate further investigations
- overdiagnosis of quiescent tumours
- can be costly and cause morbidity

- false-negative gives false reassurance
- may encourage unhealthily behaviour if negative

(some are useful e.g. aFP in chronic liver failure patients for hepatocellular cancer)

78

.

.

79

YOUNG MALE PATIENT who present with widespread metastases..
what tumour markers do you test for? (3)

LDH, αFP, and βHCG (pregnancy test) to diagnose chemo sensitive and potentially curable germ cell tumours.

80

How does PET scanning improve CT?

Positron Emission Tomography

- often combined with CT as identifies metabolically active tissue (cancers) that the CT alone would not pick up on size alone

81

what type of cancers can immunoglobulins detect as tumour makers? (1)

paraproteinaemias (myeloma, non-Hodgkin's lymphoma)

82

three purposes of surgical oncology (3)

1. Diagnosis and staging (biopsy)
2. Treatment of cancer
3. Prevention of cancer
(e.g. colectomy in FAP and masectomy in BRCA)

83

types of biopsy (4)
why might biopsy route be important? (1)

1- fine needle aspiration cytology
2- tru-cut (core) needle biopsy – a piece of tumour is sampled under local anaesthetic, slightly higher sensitivity for some cancers than FNA
3- incisional biopsy- a piece of the tumour is sampled at surgery
4- excisional biopsy- the whole of a mass is removed

radical surgery may require removal of the biopsy track --> poorly chosen route -->more extensive and disabling operation to achieve cure
(this is particularly an issue with soft tissue sarcomas)

84

what proportion of patients with cancer receive chemo?

~60-70%
it's the one that cures the least

85

mechanism of action of chemotherapy? (2)
which cancers are more chemosensitive? (1)

wide variety of mechanisms:
- most agents target DNA either directly or indirectly
- toxic towards actively proliferating cells

- tumours which divide rapidly, with short doubling times, usually respond best to chemotherapy i.e. MORE AGGRESSIVE ones tend to respond better

although cytotoxic drugs consistently cause DNA damage, tumour cells differ with regard to their response (death or recovery) to that damage

86

uses for chemotherapy in cancer care (6)

- neoadjuvant
- primary (for a tumour that is inoperable or of uncertain operability)
- adjuvant; for occult microscopic metastases after lymph-node positive disease
- palliative
- curative; justifies more intensive treatment + greater toxicity
- prophylactic; e.g. hormonal treatments like tamoxifen before invasive carcinoma appears

some tumours likely curative e.g. germ cell tumours, Hodgkin's disease, Non-Hodgkin's lymphoma and many childhood cancers).

87

when is single-agent chemo used? (1)

usually multiple used to ensure synergism (different actions so may kill more cancer cells)

- single-agent used in palliative mainly

88

When would you administer 'high dose' chemotherapy? (2)

- long term survival
- cure (only the case in relatively few cancers, such as Hodgkins disease and Ewings Sarcoma)

- supportive care required; bone marrow support with growth factors, or 'rescue' of the bone marrow using transfusion of previously harvested blood stem cells

89

Why is maintenance chemotherapy treatment rarely used? (2)

Prolonged chemotherapy:
- increases toxicity
- resistant clones develop

90

Routes of admission of chemo? (3)
How is dosage calculated? (1)

Oral
- only some available PO
- less lengthy hospital visits required

Systemically
- bolous injection or short infusion
- some may be given continuously through peripheral or central line

Regionally
- intravesical: superficial bladder cancer
- intraperitoneal; for tumours that spread trans-coelomically e.g. ovarian
- intra-arterial; e.g. hepatic artery infusion for liver metastases
(high dose to site of tumour and less systemic toxicity)

most calculated by BODY SURFACE AREA (DuBois calculation)
renal function or body weight for some

91

myelosuppression in chemotherapy:
- how does chemo cause myelosuppresion? (1)
when does it occur? (1)
- lowest point called...? (1)
- what cell count is a/w clinical infection? (1)

- killing haematopoietic progenitor cells --> leucopenia and thrombocytopenia

- 10-14 days post beginning of each cycle
(recovers 3-4 weeks --> another cycle commences)

- nadir
(as progenitors recover the peripheral counts return)

- 1 x 10^9/1 = clinical infection
- 0.5 x 10^9/1 = significant

92

causes of myelosuppression in cancer? (4)
which treatments cause it? (2)

1- treatment
2- bone marrow infiltration -->pancytopenia
3- para-neoplastic syndromes can --> pancytopenia or falls in single haematopoietic lineages
4- other e.g. anaemia from iron def. or chronic disease (-->anaemia) often macrocytic but not megaloblastic

- chemotherapy
different agents have differential effects on different components of the bone marrow
e.g. carboplatin cause relatively more thrombocytopenia
- biological therapies such as interferon and interleukin-2
but mechanisms and kinetics differ from that caused by conventional chemotherapy

93

investigation of myelosuppression? (4)
when to investigate? (1)

- blood film
- measurement of haematinics (nutrients needed for erythropoiesis e.g. iron, B12, and folate)
- bone marrow aspirate
- trephine (biopsy)

- investigate if longer than a transient nadir

94

three types of myelosuppression? (3)
which is most dangerous? (1)

in anaemia: when to consider blood transfusion? (1) other treatment option? (1)
(others on another card)

- anaemia
- thrombocytopenia
- neutorpenia

- NEUTROPENIA most frequent cause of mortality and morbidity a/w myelosuppresion

- if <10g/dL then consider blood transfusion
- consider recombinant erythropoetin

95

clinical signs of thrombocytopenia? (4)
when to treat thrombocytopenia? (3)
problems with platelet transfusions? (2)

- petechial haemorrhage ( tiny, circular, non-raised patches)
- spontaneous nose bleeds
- corneal haemorrhage
- haematuria

- thrombocytopenia defined as < 150 x 10^9/L

- < 10 x 10^9/L = risk of spontaneous bleeding e.g. intracerebral hemorrhage, with a risk of irreversible disability--> URGENT platelet transfusion

- 10 x 10^9/L tp20 x ^109/L = platelet transfusion, particularly in the presence of other complications such as infection

- > 20 x 109/L, in the absence of spontaneous bleeding, do not routinely require platelet transfusion.

- repeated platelets --> specific antibodies to blood cells ---> failure to increase platelet counts immediately after transfusion (platelet transfusions don't last long)
- need a single donor (rather than pooled) or HLA matched platelets.

(chemotherapy or radiation treatment, or from the underlying disease itself)

96

how to treat neutropenic sepsis? (2)
what if no response to treatment? (2)
what happens if untreated? (1)
what to do if asymptomatic? (1)
what to avoid in neutropenia? (1)

- broad-spectrum IV Abx if fever/unwell post-chemo IMMEDIATELY
- then cultures of blood, urine, sputum, throat etc. and a chest X-ray + adjust Abx accordingly
i.e. BUFALOS and ABCDE
- growth factors and admission to intensive care
- use MASCC criteria to decide if they can go home

- if doesn't respond to Abx in 2 days, go to 2nd line
- then consider atypical infections (pneumocystitis pneumonia PCP) or systemic fungal or viral infections

- most frequent cause of mortality and morbidity a/w myelosuppresion as --> organ failure and septic shock

- asymptomatic can be left but closely observed

- avoid vaginal/ rectal exams as will --> bacteraemia if mucosa breached

97

methods of prevention of myelosuppression? (3)

- prophylactic antibiotics (rarely used)
- dose modifications; if you're using curative therapy though obviously try to make patient tolerate it if possible
- colony stimulating factors e.g. G-CSF (granulocyte-colony stimulating factor)

98

side effects radiotherapy specific to:
(a) head and neck
(b) prostate
(c) lung

acute = -itis (inflammed)
chronic = -osis (scarred tissue)

H&N:
- mucositis
- skin reaction (radiation dermatitis)
- thick oral secretions
- loss of taste
- fatigue
- dry mouth
(remember guy saying he hated eating and talking on radio was difficult with dry mouth)

PROSTATE:
- prostatitis
- cystitis
- haematuria/ mucus
- abdo pain
- nausea

LUNG:
- cough
- SOB
- chest pain
- rarely nausea
- pneumonitis

99

characteristics of screening tests in terms of:
tumour? (5)
test? (6)

- be curable when detected early
- relatively common
- long pre-invasive or non-metastatic stage
- detect relatively simple tests
- be distinct from benign lesions

- specific
- sensitive
- well publicised to ensure high uptake
- well tolerated
- able to detect early enough to implement effective treatment
- easy to administer/ perform

NO ideal screening tests exist

100

Screening:
potential advantages? (4)
potential disadvantages? (4)
ways to mitigate problems? (2)

- less radical treatment--> reduce morbidity
- reduce mortality
- saving health resources by increased cure rates
- reassurance of negative test

- increased anxiety/morbidity if no effective intervention possible
- over-investigation of false +ves
- over-treatment (prostate)
- harmful effects of screening
- cost of screening

- only screen "at-risk" populations --> improve sensitivity and specificity and more effective targeting of test which increases compliance
- develop an effective infrastructure e.g. via primary health care teams, support groups and work places to increase awareness and uptake of at-risk populations

(genetics tests could be used in future in who to screen but ethical concerns! i.e. do we really need to know if we are slightly at risk of something and cause anxiety)

101

screening:
which programmes available in UK currently? (4)
ages? (3)
what is done? (3)
why is cervical smears particularly effective? (1)
which other cancer being investigated for screening? (1)

- cervical: 25-50 for "cervical smears" every 3 years, then 50-65 every 5 years, then over that if abnormal one
- breast: 50-70 for mammography every 3 years (controversial outcomes)
- colorectal: 60-74 FOB every 2 years, now changed to FIT (faecal immunochemical test kit), those 55+ invited for one-off bowel scole flexible sigmoidoscopy
- prostate cancer has an 'informed choice' programme at GPs so not really screening (over-treatment risk)

At risk patients, such as those with ulcerative colitis, a strong family history or a previous primary tumour should be screened within their existing management plan including regular colonoscopies.

- cervical cancer: relatively long pre-invasive period during which early detection can occur, and for which an effective treatment can be offered

- ovarian cancer (CA125) being investigated

102

communication of bad news:
framework? (1)
what is important? (11)

SPIKES
Important to know WHAT the patient wants to know and TELL THEM exactly what they want
(note: some might not want to know they have cancer so BEWARE!)

- what do they know at the moment?
- give info in stages and let them ask questions in between/ pause so they can stop the discussion if he/she does not want to know any more

- eye contact
- relaxed posture
- patient can answer questions
- allow sufficient time
- be prepared: know the patient background well
- may need close friend/relative near or with them
- be honest + don't give false reassurance
- no jargon
- identify if referral for psychological support is necessary

103

Oncology:
When discussing prognosis to a patient, how should you do this? (3)
what to do to retain hope? (1)
what might be reassuring to know for them in terms of when they will die? (1)

"We want to hope for the best, but plan for the worst"

1- set realistic goals for any intervention, whether curative or palliative
2- use terms such as reasonable, good or excellent to describe patients’ chances of reaching those goals
3- don't give exact life span as unlikely to be correct

- Setting achievable goals, e.g. taking a holiday, looking forward to a family event, helps to maintain hope

- the more we know about the concerns the better tailored reassurance we can give

It may be useful to assure them that sudden death is uncommon from cancer and, if the patient, or family, feel it would be helpful, give some pointers which might signify deterioration in the patient's condition and progression to a different phase of the illness, e.g. deterioration in appetite, general weakness

104

clinical trials:
how long do they take? (1)
what must be done before trial started? (1)
what does the protocol include? (5)

- 5-10 years
involves basic scientific understanding of the nature of malignancy, initial in vitro studies and animal testing

- trial protocol

- inclusion/ exclusion
- objectives
- background info (previous trials/ animal trials)
- management plans of expected toxicities
- ensure sample size enough (power calculations) to avoid false negatives due to random variation
- ethical committee approval of protocol is mandatory

- each participant must give written, informed consent
- trials must comply with accepted codes of practice e.g. GCP (Good Clinical Practice)

105

clinical trials:
what are the three phases? (3)

PHASE 1:
'Is it safe in people?'
- determine toxicity (previously tested in vitro and in animals)
- establish maximum tolerated dose (MTD)
Disease response is not an endpoint, so drugs with no clinical activity seen are not rejected at this phase
- Dose escalation is performed, commencing at 10% of the dose (/kg) that is lethal in 10% of mice (‘LD10’).

PHASE 2:
'Does it treat the disease?'
- aim is to assess the particular anti-tumour activity of a new treatment in a range of different cancers
- radiological tumour shrinkage (‘response rate’) is the primary outcome measure

PHASE 3:
'Is it more effective than standard therapy?'
- RCTs comparing new and established treatments
- endpoint usually 'overall survival', 'response rate'/QoL are often secondary
- large sample size needed for small improvement in treatment --> often run in multiple centers in multiple countries

106

In clinical trials, how do you measure the following response end points:
- tumour growth/ shrinkage and 'response? (1)
- survival? (3)
- toxicity? (1)
- what outcome particularly important in palliative trials? (1)

- RECIST; response evaluation criteria in solid tumours
- classified into categories, see other slide

- overall survival: length of time entry to trial and death from whatever cause
- disease free survival: between entry to trial and recurrance or tumour or death from other causes
- pregression free survival: time between entry to trial and disease progression/ reoccurence

- WHO toxicity criteria: 4 grades= 1(least) --> 4(most)

- QoL of particular importance in palliative treatments

107

Tumour response rate:
what is a "target lesion"? (1)
how are they measured to define treatment response? (2)
what do you do with the other lesions? (2)
what's the use of identifying target lesions? (2)

- all MEASURABLE lesions

- longest diameters are measured at baseline (up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs)
- calculate sum of these for all target lesions

- all other lesions (or sites of disease) should be identified as non-target lesions and be recorded at baseline but not measured
- note the presence/absence of each throughout follow-up

- after treatment, define target lesions according to criteria (complete response, partial, stable and progressive)
- criteria used (30%/20% thingy used) is dependent on SUM of LENGTH DIAMETERS of TARGET LESIONS compared to reference the baseline sum LD

Note:
'intention-to-treat' used to minimize selection bias in loss to follow-up of studies
(unsure why this is on this card but useful fact!)

108

clinical trials:
how to calculate sample size?

- calculation to ensure enough power to detect significant result
- if small effect at high significance, a larger cohort will be needed

to detect a 20% response rate of a new cancer treatment, as few as 14 patients are required: the probability of the first patient not responding to the drug is 0.8, the first two patients 0.64 (0.8 x 0.8), the probability of all 14 patients failing is less than 0.05 (=0.814). Therefore if no responses are observed with 14 patients the treatment can be assumed with 95 % confidence, to have a response rate less than 20%

109

What are the survival curves called?

Kaplan Meier Curves
- median survival and survival rates for example 5 year survival, can be estimated

110

what are the following novel trial designs:
basket trials (1)
umbrella trials (1)
platform trials (1)

- where tumours harbouring a particular genetic mutation (of whatever primary site) are tested with a new drug that targets that mutation.

- where patients with a particular type of cancer (e.g. non-small cell lung cancer) are all tested to establish the genetics of their tumours and then offered different experimental treatments depending on the results.

- where multiple experimental arms are compared with a single control arm to reduce costs and increase the number of patients able to receive novel therapies.

The hope is that these trial designs will save money and yet produce more rapid answers. They may also be “adaptive” (ie allow unsuccessful arms of studies to be dropped early and potentially replaced by something else that has become available since the trial started).

111

Definition of quality of life? (3)
what aspects does in include? (5)
how do you measure it?

- SUBJECTIVE evaluation of life as a whole

- patients' appraisal of and satisfaction with their current level of functioning compared with what they perceive to be possible or ideal
- physical, mental and social well-being, not merely the absence of disease or infirmity (WHO)

1- PHYSICAL FUNCTION: self-care activities, functional status, mobility, physical activity, household activities
2- DISEASE + TREATMENT SYMPTOMS: specific symptoms e.g. pain/ SOB/ side effects of treatment
3- PSYCHOLOGICAL functioning: emotional distress, anxiety, depression (may be 2o to disease)
4- SOCIAL FUNCTIONING: family interactions, time with friends, recreation activities
5- OTHERS e.g. spiritual, cognitive, sexual function, body image, satisfaction with care

HAD and Rotterdam criteria have superior detection rate to that of doctors/nurses

112

Quality of life instruments? (4)

1. Generic. i.e. for people with health problems but not specifically designed for cancer patients. This category includes Medical Outcome Study (MOS) Short Form (SF)-36.
2. Cancer specific. e.g. EORTC QL Questionnaire Core-30 and the ‘FACT’ (functional assessment of cancer therapy).
3. Cancer site specific. Includes, for example, Breast Cancer Chemotherapy Questionnaire, EORTC Lung Cancer Module.
4. QL domain specific instruments.

113

Important observations about QoL and oncology (5)

- aggressive anti-cancer treatment can --> improved QL as decreases impact of cancer

- more effective therapy is usually associated with better QL even if more intensive and associated with toxic effects.

- patients may report an improved QL despite showing no objective tumour shrinkage on CT scanning. This could be related to reduction in circulating tumour factors such as tumour necrosis factor, minimal shrinkage of tumour, giving relief to symptoms, to increased medical attention or to provision of hope.

- descriptive studies have confirmed the clinical feeling that symptoms of cancer are associated with quantifiable disruptions in QL.

- pre-treatment QL status may predict survival, independently of other more traditional medical measurements.

114

meaning of:
QALY? (1)
Q-TWiST? (1)

QALY (quality-adjusted life years) of survival

Q-TWiST (Quality adjusted Time Without Toxicity and Symptoms)

115

Hypercalcaemia:
how do tumours cause calcium increase? (3)

1- bone metastasis
AND release factors which increase bone resorption and increase renal tubular calcium re absorption:
2- tGFA: transforming Growth Factor Alpha (stimulates bone resorption)
3- PTHrP: Parathyroid hormone (PTH) related peptides (acts like PTH) in lung cancer (NSCLC)

116

hypercalcaemia effects:
how to assess? (1)
general? (4)
CNS? (5)
cardiac? (7)
geniturinary? (1)
GI tract? (7)

- head-to-toe assessment (same a neutropenic sepsis!)

- dehydration
- weakness
- fatigue
- bone pain

- confusion
- seizures
- proximal neuropathy
- hyporeflexia
- coma

- bradycardia
- short QT
- wide T wave
- prolonged PR interval
- BBB
- arrythmia
- arrest

- polyuria

- weight loss
- nausea
- constipation
- abdo pain
- ileus
- dyspepsia
- pancreatitis

117

Imaging:
what is fluoroscopy? (1)
applications of fluoroscopy? (4)
the benefit of ultrasound over x-ray? (2)
which imaging technique has similar benefits to ultrasound? (1)

- "x-ray movie" / live x-ray
- used in: GI, urological, orthopaedic, vascular (angiograpy/ angioplasty)

- ultrasound has ionising radiation and shows soft tissue better

- MRI also has no radiation but complex and slow and slightly less available than others, MRI is also good for soft tissue

118

Radiology:
what is nuclear medicine? (1)

- radiation ++
- different radiotracers are given to patient, then body gives off gamma rays
- gamma camera + CT (SPECT-CT)

119

Biological therapies:
how do mutations in cancer lead to metastasis/ excess growth? (1)
how do biological therapies use this to their advantage? (1)

- cells either gain mutations that promote cell growth or lose genes that control growth

- biological therapies target growth pathways --> reduced growth

- every year more and more becoming available
- treatments more personalized to individual cancers
- have very different side effects to chemo

120

Hormone therapy:
which cancers are most susceptible to this treatment? (6)
(sex hormones (3) and corticosteroids (3))
what part of treatment is hormone therapy used in? (4)

unsurprisingly.. those arising from tissues under hormonal control of normal cellular proliferation or survival

Sex hormones:
- prostate
- breast
- endometrium

Corticosteroids:
- lymphocytic malignancies
- lymphoma
- leukaemia
- myeloma

- neo-adjuvant
- primary treatment
- adjuvant therapy
- palliative

treatment aims to adjust the hormonal "environment" of the cancer cell..Interference with this system may involve removing the hormone, introducing a competing molecule or modulating the receptor

121

Hormone therapy:
Types? (3)
how can you remove the source of growth-producing hormone? (2)
which group are these techniques inappropriate for and why? (2)
what can you do in this group instead? (1)

1- remove source of growth-promoting hormone
2- hormone inhibitors
3- increasing hormones

- surgical castration: bilareral oophorectomy (in pre-menopausal/ orchidectomy
- medical castration: long-acting LHRH analogues which block LH and FSH production

- unsuitable for postmenopausal women as sex hormone in extra-gonadal (fat/ adrenal glands)

- aromatase inhibitors: stop the rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase
(androstenedione is secreted by adrenal and aromatized in other tissues (fat and liver))

122

Hormone therapy:
what hormone inhibitors commonly used in cancer? (2)

- tamoxifen acts like anti-oestrogen (stops it attaching)

- anti-androgens: two main types

1. steroidal anti-androgens (e.g. cyproterone acetate) have a dual action. In tumour cells they inhibit the androgen receptor, but in the hypothalamus they substitute for testosterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release.

2. non-steroidal anti-androgens (e.g. bicalutamide) inhibit testosterone in both tumour cells and hypothalamus, so feedback inhibition is lost and serum testosterone levels rise. "Maximum androgen blockade" describes the combination of a non-steroidal anti androgen with an LHRH analogue to prevent this effect and is used as a therapeutic strategy in prostate cancer.

123

Hormone therapy:
when is increasing hormones useful in cancer treatment?

- high glucocorticoids induce apoptosis in some malignant lymphoid cells, and form an important component of treatments for lymphoid leukaemias, lymphomas, myeloma and Hodgkin's Disease.

- used in certain sex-hormone sensitive cancers with the aim of inducing negative feedback loops (e.g. oestrogens to down-regulate hypothalamic LHRH in prostate cancer) or tachyphylaxis (down-regulation) of receptors (e.g. high-dose oestrogens in breast cancer).

- Progestogens are synthetic analogues of progesterone (e.g. medroxyprogesterone acetate; megestrol acetate), which may be given orally in high dose for cancers arising in progesterone-sensitive tissues (breast, endometrium). They may give direct inhibition of tumour growth via acting as an agonist of the progesterone receptor, but also produce negative feedback on the pituitary/gonadal axis. These drugs may also stimulate the appetite and are widely used in palliative medicine for that reason.

124

Radiotherapy:
principles of how it works? (1)
how is it delivered? (1)
is palliative radiotherapy given in more or less fractions? (1)

ionizing radiation causes damage to DNA repair mechanisms - normal cells can repair themselves but cancer can't

several small doses (fractions)

palliative radiotherapy is delivered in smaller number of fractions to a lower total dose (e.g. 8Gy in 1 fraction or 20Gy in 5 fractions for instance) instead

125

Radiotherapy:
what is toxicity and treatment effect dependent on? (3)
what is the therapeutic index? (1)
why is chemo sometimes given concurrently? (1)

ON ANOTHER SLIDE (but read again..)

1- TREATMENT issues: total dose, total volume treated, dose per fraction, overal treatment time

2- CO-MORBIDITIES (diabetes/ IBD), smoking

3 RADIOSENSITIVITY of the cancer cells (seminoma and Hodgkin's disease are highly radiosensitive and respond well to low doses of radiation whereas cancers such as a glioblastoma multiforme are relatively radio-resistant to even high doses of radiotherapy), tumour hypoxia, tumour re-population and additional treatment such as chemotherapy.

- balance between tumour control and the side effects of radiotherapy

- concurrent chemotherapy and is thought to act as a radiosensitiser, which means it increases the sensitivity of the cells to radiation (improves efficacy without having to increase dose) but can -- > increased side effects

126

Radiotherapy:
describe it to the patient? (5)

can't see, can't feel, can't hear

- planning scans
- sit still
- x-ray machine will move around you
- patients are reviewed at set points through their radiotherapy to ensure side-effects are managed appropriately.

and as with other treatment mention ATHLETICS
Action, Timeline, How to take, Length of treatment, Effective-time before, Tests, Important side effects, Complications, Contraindications, Supplementary advice

127

Radioisotopes:
what is the most common form? (1)
why doesn't this affect surrounding tissue? (1)
how do you prevent radiation going to others? (1)

- radioactive iodine, I-131 in thyroid cancer:
take up by thyroid and concentrated in any remaining thyroid tissue, normal or malignant, where it emits radiation as it undergoes radioactive decay, ablating the thyroid cells.

- few other tissues in the body take up iodine --> selectively delivery

- pt. remains in the lead lined room until the level of radiation they are emitting is low enough to be safe to others ~4 days

128

Radiotherapy:
two recent developments? (2)
what do each entail? (2)

- stereotactic radiotherapy:
when a small, well-defined tumour, you give a large dose of radiotherapy to a small "margin"
(can replace surgery in patients with increased risk factors for surgery)
v. good for brain

- intensity modulated radiotherapy (IMRT) and "Arc therapy":
a small number of beams (often 3 or 4), aimed at the target volume in the patient from different directions and shaped to match the target from each direction using the MLC collimator leaves within the treatment machine
machine moves in an arc around the patient
--> very fast

129

Chemotherapy side effects:
neurological (4)

- peripheral neuropathies:
(remember that lady who uses pen to write on her phone)

- autonomic neuropathy

- central neurological toxicity

- ototoxicity:
cochlear damage rather than auditory nerve damage --> high tone hearing loss

130

Chemotherapy side effects:
genitourinary? (2)

1- nephrotoxicity: platinum agents, principally cisplatin, and with the alkylating agent ifosfamide. The renal excretion of many cytotoxics means that adequate renal function is required to reduce overall toxicity.

2- bladder toxicity: Cyclophosphamide and ifosfamide cause haemorrhagic cystitis in a dose-dependent manner. Antidotes exist, such as Mesna.

131

Chemotherapy side effects:
cardiac (2)

- acute arryhtmias
doxorubicin and paclitaxel

- coronary artery spasm (and --> cadiac ischamia)
5-FU and related drugs such as capecitabine

132

Chemotherapy side effects:
skin and soft tissue (4)

1- EXTRAVASTATION:
some are highly vesicant
- administered through fast-running drips under direct observation, to dilute any vesicant action and to make nurses aware immediately if it occurs
- antidotes used immediately if occurs

2- PALMAR PLANTAR ERYTHEMA (Hand-foot syndrome):
erythema frequent with 5-FU, capecitabine and some of the targeted agents e.g. sunitinib, erlotinie, unknown cause
- emollients
- drug withdrawal
- review person for other SEs of drug e.g. bowel toxicity

3- PHOTOSENSITIVITY:
e.g. 5-FU --> use high-factor sun blocks.

4- PIGMENTATION:
Bleomycin--> skin and nail pigmentation in combination with pulmonary fibrosis

NB: with chemotherapy lots of different side effects and different chemo causes different effects to lesser/greater extents

133

Chemotherapy side effects:
long term complications? (2)

1: Second malignancies
- sub-lethal DNA damage --> genetic changes --> second malignancy
- most common in alkylating agents and procarbazine
- frequency expected to increase as more long-term survivors following curative or adjuvant therapy
- more common in high-dose therapy

3: Pulmonary
- long-term pulmonary damage from fibrosis induced by drugs such as bleomycin and busulphan
- high-dose or prolonged administration of most alkylating agents is associated with pulmonary fibrosis or pneumonitis

134

Cancer immunotherapy:
how is immunosupression linked to cancer incidence?

--> increased risk of cancer
- research models support a role for the healthy immune system in cancer surveillance and prevention
- subtle phenotypical and functional deficits in innate and adaptive immunity in adults can correlate to recurrence risk and/or survival

read more on this in the blue book

135

Myelosuppression:
how do you manage it? (1)
what do you have to consider? (1)
do you give prophylaxis? (1)
or colony stimulating growth factors? (1)

- reduce dose of chemo if v severe
but....

- In patients receiving potentially curative chemotherapy such as Hodgkin's disease and testicular cancer every effort is made to maintain dose intensity but in palliative you're more likely to favour dose reduction

- prophylaxic antibiotics not normally indicated unless certain conditions e.g. presence of chronic obstructive airways disease and the use of co-trimoxazole in patients with lymphoma at risk of PCP.
- The routine use of elective colony stimulating factors to prevent or reduce neutropenia is not proven to be of benefit. In some patients such use is appropriate as they enable dose intensity to be maintained.

- role of erythropoietin also continues to be investigated

- Thrombopoietin (a platelet growth factor) has recently been described and is being assessed in early clinical studies.

136

Tumour markers most common cancer:
CA-19-9? (1)
CA-15-3? (1)
CEA? (1)
what does CEA stand for? (1)
calcitonin? (1)

- pancreatic

- breast

- colorectal
Carcinoembryonic Antigen (CEA)

- medullary thyroid cancer (as this is where the parafollicular cells are that make calcitonin)

137

Most common presenting symptom of:
MSCC? (1)
SVCO? (1)

- back pain
- breathlessness/dyspnoea

138

Most common site of bone metastasis? (5)
most common cancers? (3)
features on investigation? (4)

in descending order:
- spine
- pelvis
- ribs
- skull
- long bones

1. prostate
2. breast
3. lung

- pain
- pathological fractures
- hypercalcaemia
- rasied ALP

139

Investigating metastatic disease of unknown primary:
what investigations to do on everyone? (4)
what further investigations to do if:
lytic bone lesions (1)
abdo symptoms? (1)
men? (1)
women with ascietes/ peritoneal malignancy? (1)
in men with germ cell tumours? (1)
women with Sx compatible with breast cancer? (1)

- FBC, U%E, LFT, calcium, urinanalysis, LDH
- CXR
- CT of chest, abdo, pelvis
- AFT and hCG

- Myeloma screen
- Endoscopy
- PSA
- CA 125
- Testicular US
- Mammography

140

Biological or targeted therapy:
how do they work? (1)
what are two common examples? (2)
when do side effects occur? (2)
what to do? (2)

target division pathways

1- monoclonal antibodies (-MAB)
2- tyrosine kinase inhibitors (-IB)

- 6-8 weeks after starting treatment BUT can be up to 6 months

- lifelong hormone replacement is usual
Be wary: clinical situation can change rapidly

Low threshold steroid/ immunosuppression

Exclude infection

give high-dose steroids for symptoms --> long term leads to side effects (sleep/ weight gain/ blood pressure/ infection) and long term side effects & iatrogenic cortisol suppression

141

Radionucleotide bone scan:
what is given to the patient? (1)
what does it show? (1)

- radiolabelled technetium is given

- shows areas of increased osteoblast activity (e.g.healing or a fracture or sclerotic metastases)
- tracer is excreted in urine --> bladder shows up

142

Common side effects of immunotherapies?

- rash
- pneumonitis
- diarrhoea/ colitis
- hepatitis
- nephritis
- myalgia
- endocrinopathies

https://minerva.leeds.ac.uk/bbcswebdav/pid-8089723-dt-content-rid-17425342_2/courses/202021_31774_MEDI4227/Cancer%20immunotherapy%20Sept%202020.pdf

143

Do we expect cancer prevalence to increase or decrease globally? (1)
Why are side-effects of chemotherapy particularly important in younger people? (1)

- expect massive increase in cancer incidence (lung cancer still most common worldwide currently)

- they live for years and years with the side-effects even if the cancer has gone

144

Difference between FOB (Faecal Occult Blood Test) and FIT screening?

Colorectal cancer screening program recently changed from FOB--> FIT
FOB: 3 samples across 3 days. Can get false positives if you eat meat due to animal blood.

FIT: 1 sample, doesn’t have the issue with animal blood. You can change the specificity and sensitivity to account for the number of endoscoposits available

145

Problems with current screening programmes:
breast cancer? (1)
bowel cancer? (1)
bowel cancer flexible sigmoidoscopy program? (1)

- argument risk outweighs the benefit (still a controversial program but you can't take away something that's already there!)

- bowel cancer screening uptake higher in high SES people --> inequalities (inethical)

- unsuitable infrastructure to support it originally! not enough endoscopists

146

NHS cervical cancer screening:
what happens if positive result? (1)

HPV tested
if -ve --> 3/5 year recall
if +ve --> checked for dyskaryosis

if dyskaryosis -->colposcopy where checked for CIN

if CIN --> options depend on stage I, II, or III

If no CIN ---> 1 year recall

147

A patient is diagnosed with pancreatic cancer and asks why there is no screening for it. How do you respond?

"All screening programmes do harm. Some do good as well"

- risk vs. benefit
- talk through the things needed for a screening programme: detectable, modifiable outcome, clinical benefit of finding it early, specificity, sensitivity, infrastructure, cost) etc

148

Screening:
What is lead time bias? (1)

the phenomenon where early diagnosis of a disease falsely makes it look like people are surviving longer

e.g. prostate cancer screening in the US makes it look like they have 88% survival compared to 45% here

149

Chemoprevention:
what is it? (1)
examples? (3)
principles? (2)

‘The use of natural, synthetic, or biologic chemical agents to reverse, suppress or prevent carcinogenic progression to invasive cancer’

e.g.
- vaccines
- dietary supplements
- oral medications

- Identification of high risk population
- Effective non-toxic prophylaxis

150

Chemoprevention:
management of women at high (1)
and moderate (1) risk of breast cancer?

OFFER tamoxifen or raloxifene for 5 years to women at HIGH risk of breast cancer

CONSIDER offering either tamoxifen or raloxifene for 5 years to women at MODERATE risk

151

Chemoprevention:
what is Lynch syndrome? (2)
management of colorectal cancer prevention Lynch syndrome? (2)

- hereditary non-polyposis colorectal cancer (HNPCC)
- most common cause of hereditary colorectal cancer
(remember woman on Macmilan podcast who had 8 cancers and had to have bowel and ovaries removed)

- NICE recommendation that aspirin should be offered to Lynch Syndrome carriers, but debate regarding dose
(study run ATM to decide dose!)
- also receive annual colonoscopies

152

Lung cancer:
most common in non-smokers? (1)

adenocarcinoma

153

Immune system:
how does a normal immune system work? (4)
why doesn't this kill cancer cells? (1)
how can adjusting the immune system help? (1)
what cancers are immunotherapy currently used in? (5)

1- antigen presenting cells (APCs) identify abnormal cells
2- APCs tell killer T cells what to look for
3- killer T cells kill abnormal cells
4- once abnormal killed, killer T cells switched off by CTLA-4, PD-1 or PD-L1

- cancer cells hide from this

- if you block the 'OFF switch' i.e. the CTLA-4, PD-1 and PD-L1

growing treatment, now used in:
- skin (melanoma)
- kidney
- lung
- breast
- haematological
(e.g. remember the OSCE with immunotherapy lady with colitis, and renal clinic with everyone on it!)

first found in 1860s when physicians noticed tumours were shrinking in those infected with erysipelas

154

Immunotherapy problems:
what can occur? (3)

- infusion reactions (cytokine release syndrome)
- side effects
- immune-related adverse events (IrAE, also called immunotherapy toxicity reactions, autoimmune-type toxicity)

155

Immunotherapy:
What is cytokine release syndrome? (1)
symptoms? (5)
treatment? (2)

large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy
- fever
- rash
- rapid heartbeat
- low BP
- trouble breathing

---> hydrocortisone
+ reduce transfusion rate
+ adapt prescription
(e.g. to include paracetamol/ ranitidine)

156

Immunotherapy:
side effects? (6)

- fatigue
- nausea (antiemetic PRN)
- dry mouth
- sore mouth
- hair thining
- water retention
- diarrhoea
- low/high BP
(remember lady on phone with v high BP)

157

Immunotherapy toxicity:
why does toxicity occur in immunotherapy? (1)
when? (2)
can it reoccur? (1)
how common is it? (1)
damaging? (1)

- takes brakes off immune system that kills cancer cells AND off the healthy immune system --> INFLAMMATION

WHEN-
- unpredictable
common in first 3 months but can be up to 2 years

- can reoccur

- severe toxicity more common in combination therapy (~50%) but still quite common in single agent (~25%)

- can cause permanent damage

- commonest: skin, colon, endocrine, liver, lung
- less common: kidneys, eyes, nervous system, heart

- STEROIDS + PPI + REFER
(oral or IV steroids)
Sometimes need further steroid-sparing immunosuppression e.g. Tacrolimus or Mycophenolate Mofetil (MMF), Infliximab

158

Immunotherapy toxicity
symptoms and treatment of:
skin? (3)
colon? (1)
liver? (1)
lung? (1)

- dermatitis
- pannicultiis (inflm. subcutaneous layer)
--> rash
+ topical or IV steroids
+ consider referral to derm

- colitis
--> diarrhoea
(rule out infective causes EBV and CMV especially)
+ loperamide
+ oral/IV seroids
+ urgent flexible sigmoidoscopy
+ consider infliximab

- hepatitis
--> fatigue, anorexia, pruritus, jaundice
+ blood tests (usually discovered on these) for non-invasive liver screen: LFT, hepatitis A, B, C, E, HIV, auto-antibodies, CMV, EBV
+ USS liver & doppler

- pneumonitis
--> SOB, cough, sputum, blood, chest pain, fever
(rule out infection)
+ bloods, sputum sample, atypical pneumonia screen, CXR, may need HRCT
+ steroids

159

Immunotherapy toxicity:
types of endocrine toxicity? (4)
how does immunotherapy affect hormone production? (1)

- hypophysitis – inflammation of pituitary gland
- thyroiditis – inflammation of thyroid gland
- adrenalitis – inflammation of adrenal gland
- insulitis – inflammation of insulin producing beta cells

- initially go HYPERacitve
then..
- go HYPOactive
--> lifelong replacement of the hormones is needed

160

Immunotherapy toxicity:
what do you to in thyroiditis?

1- initially HYPERthroid but only temporary
(weight loss, diarrhoea, menstrual changes, tremor, palpitations, restless, anxious, menstrual changes)

--> high T4, low TSH
- doesn't need carbimazole usually
- give propanolol to reduce symptoms

2- then HYPOthyroid
--> check cortisol, if low start hydrocortisone replacement first (to prevent Addisonian crisis)
--> then start levothyroxine (thyroid replacement)
- refer outpatient endocrinology

161

Immunotherapy toxicities:
what does cortisol do? (4)
what does aldosterone do? (1)
how does adrenalitis usually present? (1)
what occurs in hypophysitis? (2)

VITAL for:
- regulate BP
- regulate immune system
- balance insulin and blood sugars
- help body respond to stress

- aldosterone regulates salts in blood and helps control BP

- usually don't see it OVERactive..
- presents UNDERactive gradually or acute adrenal crisis (addison's)

- in hypophysitis hydrocortisone and thyroid replacement needed (underactive pituitary)

162

Immunotherapy toxicities: hypoadrenalism symptoms? (7)
symptoms in Addinsonian crisis? (5)
how to manage crisis? (2)
what to investigate? (3)

- weakness
- weight loss
- fatigue
- skin pigment changes
- abdo pain
- cramps
- mensutral changes
- diarrhoea/ constipation (fluctuating)
- N&V
- postural hypotension
- salt craving

MEDICAL EMERGENCY
- N&V
- abdominal pain
- dehydration
- dizziness/ low blood pressure
- collapse
---> 999, IV/IM hydrocortisone at scene

- do immunotherapy bloods
- cortisol level
- cortisol stress test/ repeat test ltare

163

Immunotherapy toxicities:
what is a standard hydrocortisone replacement treatment? (1)
what do you need to tell patients when starting on steroids? (5)

- 10mg AM
- 5mg lunch
- 5mg teatime
(minimics bodys usual steroid production)
Pharmacy will give steroid alert card

1- give leaflet/ refer to websites e.g. patinet.info
2- inform steroids shouldn't be stopped
3- inform of sick-day rules:
double dose of steroid in time of stress for at least 2 days until feeling better
if vomit within 30 mins then take dose again
4- if unable to take them seek urgent medical advice

5- refer outpatient endocrinology for rescue pack (IM hydrocortisone)

164

Immunotherapy toxicities:
insulinitis is how common? (1)
symptoms? (4)

- rare
(effectively immunotherapy induced type 1 diabetes!)

- polydipsia
- polyuria
- fatigue
- diabetic keto-acidosis
MEDICAL EMERGENCY

-> urgent assessment
- CAP glucose
- ABG
- urine dip and protein creatinine ratio
- full immunotherapy bloods
- refer diabetes team

165

Immunotherapy toxicities:
nephritis symptoms? (3)
myocarditis?
nervous system?

(just be familiar with presentation)

- decreased urine output
- frothy urine
- rarely bloody urine

- rule out other causes with dip and protein creatinine ratio

- palpitations, chest pain, postural hypotension,SOB< cardiac failure
- ECG, troponin, ECHO, cardiology

- pins and needles, weakness, foot drop, eye symptoms/ palsies, headaches, progressive symptoms (Guillian-Barre, Myasthesia Gravis), SOB, bulbar palsy

166

Gynaecological cancers:
types? (4)
and basic description of each? (4)

1- endometrial: COMMON but CURABLE (women recognize symptoms early)

2- ovarian: "SILENT KILLER" but not really that silent...

3- cervical: "chaotic single mother" as HPV and not up to date on smear

4- vulval: uncommon

167

Ovarian cancer:
is it curable? (1)
what treatment is best? (1)

High grade:
- CHEMOSENSITIVE- chemotherapy reduces it down
- but often comes back

Low grade: not many treatment options... "like pouring glue into the abdomen", grows slowly but stops everything running normally

168

When can neutropenic sepsis occur?

normally occurs 5-7days after (that's when the nadir is), can be within 3 weeks of receiving chemotherapy

169

Chemotherapy:
what happens if someone is allergic to it?

- if there is no alternative then you stop giving it, let them recover, then try giving it to them again!! (limited options)
- attempt to desensitize

170

BRCA 1 and BRCA 2 mutations:
what do they increase risk of: BRAC1 (2) and BRCA 2? (5)
when do you test for these genes? (3)
what happens if someone has the gene? (2)

BRCA 1 = breast, ovarian
BRCA 2 = breast, ovarian, prostate, pancreatic, melenoma

Refer to genetics for blood test/ check tumour biopsy to check for mutation if risk of mutation is >10%, i.e. if
- pt has rare cancer e.g. peritoneal
- high FH of breast cancer (certain scoring system as it's such a common cancer so one or two women in family getting it age 60 could just be coincidence)
- family member has tested positive, then you test everoyne in their immediate family

- if young may consider bilateral mastectomy
- regular monitoring e.g. yearly mammography

- BRCA 1 breast cancer is often triple negative

BRCA is a tumour suppressor gene --> mutation increases cancer risk

171

Performance status:
what are the categories? (5)
what do they each mean? (5)

0= normal
1= symptomatic & ambulatory cares for self
2= ambulatory >50% time
3= ambulatory <50% time nurisng care required
4= bedridden

a patient of poor performance status may be unsuitable for chemotherapy or surgery, and less likely to be on radical treatments (curative)

172

Colorectal cancer:
which treatments can you do out of surgical, chemotherapy and radiotherapy? (1)

Surgical then adjuvant chemotherapy is the main treatment. Radiotherapy has little role in colorectal, better in rectal cancer.

173

Painless haematuria in the absence of UTI symptoms (LUTS)... what is your top differential? (1)
most appropriate INITIAL investigation? (1)
what to do in GP land? (1)

- bladder cancer

--> urine dipstick to exclude infection
- referral to urology 2-week wait if no infection or haematuria persists after treatment

174

what cancer treatments increase risk of VTE? (2)

- cancer itself increase VTE risk but also..

- CHEMOthreapy
- tamoxifen