Oncology

Question 1

What is chemotherapy in general?

Answer 1

Group of cytotoxic agents used to SYSTEMATICALLY manage cancer

Question 2

Why is it necessarily for chemo to systemically Tx patients, rather than being just localised?

Answer 2

Metastasis kills patients, not local recurrence in primary organ

Question 3

What is the % of people with cancer who will require chemotherapy?

Answer 3

60-70%

Question 4

What is the mechanism by which chemo exerts its anti-cancer action?

Answer 4

Most target DNA directly/indirectly

Preferentially toxic to actively proliferating cells ∴ work best on rapidly dividing tumours

Question 5

What are the uses for chemo?

Answer 5

• NEOADJUVANT - Tx of operable tumour pre-op to reduce its size ∴ allow for less radical Tx. Also Tx micro mets.
• PRIMARY - initial Tx for inoperable tumour - reduce tumour bulk to allow surgical resection (↑ cure rates)
• ADJUVANT - post op Tx for micro mets after complete resection (↑ cure rates)
• PALLIATIVE - relieve Sx and prolong life when incurable. Balance so not to ↓ QoL
• CURATIVE - mostly germ cell, (non)Hodgkin’s lymphoma, childhood cancer WITHOUT surgery, even with mets! ∴ justifies intensive Tx with ↑ toxicity
• PROPHYLACTIC - hormonal Tx before overt malignancy appears e.g. tamoxifen for in-situ breast cancer before invasive carcinoma

Question 6

Cytotoxic chemo is most commonly given in combo of different drugs. Why is this?

Answer 6

1. Different mechs of action give highest chance of result (several sub-lethal cell injuries can kill cell in combination- synergism)
2. ↓ chance of drug resistance
3. Different drugs = different toxicity effects ∴ dose can be maintained

Question 7

How are most schedules of chemotherapy treatments given?

Answer 7

Cyclically - every 3-4 weeks

Question 8

Why are chemotherapy treatments scheduled cyclically (i.e. every 3-4 weeks)?

Answer 8

Allows normal cells to recover from toxicity - low blood counts (myelosuppression) and mucositis

Repeated cycles required for full clearance as only a proportion of tumour cells killed each time

Question 9

Why are many chemotherapy treatments only maximally effective after a 6 month course?

Answer 9

Due to resistance emergence (chemo sensitive die and resistant remain ► replicate) and increased toxicity

Question 10

Why do most people with cancer take conventional doses of chemotherapy?

Answer 10

Known to be effective against the particular malignancy in majority of PTs

Side effects are tolerable

Question 11

Why is it bad to take high doses of chemo?

Answer 11

Higher toxicity, and potentially lethal SEs (1-2% mortality) (bone marrow suppression) → specialised supportive care required (GFs, rescue stem cells/bone marrow, ABx)

Question 12

What cancers are ones where high doses of chemo are justified?

Answer 12

High doses justified only when long term survival or cure possible (HELL-MUG):

Hodgkins

Ewing’s sarcoma

Leukaemia

Lymphoma

MUltiple myeloma

Germ cell tumours of testis

Question 13

Why is prolonged chemotherapy to maintain remission not advised/advantageous?

Answer 13

Increased resistance and toxicitiy

Question 14

What condition/group of patients is maintenance chemotherapy advised?

Answer 14

Childhood Leukaemia - 18 months maintenance Tx post remission

Question 15

What is the advantage of giving chemo orally?

Answer 15

Freeing the patient from lenghty hospital visits and invasive procedures

Question 16

What is the disadvantages of taking chemo orally?

Answer 16

1. Doesnt reduce toxicity - requires regular review
2. Only few chemo drugs avaliable orally (cyclophosphamide, etoposide, capecitabine, tamoxifen)
3. Absorption issues can effect levels in circulation

Question 17

How is most chemotherapy given?

Answer 17

IV mostly as bolus injection or short infusion.

Can be continuous infusion via central line

Question 18

Chemotherapy Tx can be administered regionally. What are the methods?

Answer 18

Intravesical - high doses given at site, ↓ systemic absorption and toxicity e.g. superficial bladder cancer

Intraperitoneal - for trans-coelomically spread tumour e.g. ovarian cancer

Intra-arterial - for tumours with well-defined blood supply (e.g. hepatic artery infusion for liver mets). ↑ doses to involved site ↓ systemic absorption

Question 19

How are chemotherapy doses calculated?

Answer 19

Most calculated according to patients body surface area (DuBois and DuBois formula):

BSA = (Weight (kg) 0.425 x Height (cm) 0.725) x 0.007184

Others:

• Carboplatin - renal function
• Newer drugs e.g.traztuzumab - body weight

Question 20

What type of ADVANCED cancers is chemo most effective (i.e. cure of advanced disease in >50%)

Answer 20

Hodgkins disease

Testicular/germ cell cancers

Acute lymphoblastic leukaemia

Choriocarcinoma

Paediatric cancers e.g. leukaemia, lymphoma, sarcoma

Question 21

What are the ADVANCED cancers where chemo is less effective (<50% cure)

Answer 21

Non-Hodgkins

Ovarian cancer

Paediatric Neuroblastoma

Osteosarcoma, Ewings Sarcoma, Rhabdomyosarcomas

Question 22

What types of REGIONAL cancers will chemo increase cure rates?

Answer 22

Breast

Colorectal

Non-small cell Lung

Oesophageal/gastric

Bladder

Question 23

What types of cancer will chemo result in remission in most pts?

Answer 23

Those in list of curable cancers.

Breast

Small cell lung cancer (very chemo sensitive)

Ovarian cancer

Question 24

What types of ADVANCED REGIONAL cancer will chemo prolong survival but NOT cure in most?

Answer 24

Non-small/small cell lung cancer

Colorectal cancer

Gastric cancer

Breast cancer

Bladder

Prostate

Question 25

What types of cancer is chemo only really effective for pallitation of Sx?

Answer 25

Renal Cancer Melanoma Head and neck cancer Pancreatic Billiary Tract cancers

Question 26

What are the IMMEDIATE GI SEs of chemotherapy

Answer 26

**N&V** - direct stimulation of vomiting centre, peripheral stiumlation and anticipatory. **GI -** rapidly dividing cells ∴ susceptible. * **Mucositis** (especially oral) * **Diarrhoea** (colitis/inflammation) * **Constipation** (dehydration, other drugs e.g. opioids)

Question 27

What are the IMMEDIATE bone marrow related SEs of chemotherapy?

Answer 27

**Myelosuppression - kills haematopoietic progenitor cells.** * ↓WCC (\< 1 x 10⁹), ↓platelets (rare if standard doses used) - after 10-14 days. * Higher doses - cause worse/longer leucocyte fall (but drug dependent) * Lowest point of drop = nadir. * Recovery after 3-4 weeks.

Question 28

What are the immediate hair related SEs of Chemo?

Answer 28

Alopecia - hair follicles rapidly dividing (reversed with discontinuation) - ↓ with cold cap

Question 29

What are the immediate neurological SEs of chemotherapy?

Answer 29

* **Peripheral/Autonomic neuropathies** (mainly sensory) (e.g. cisplatin, taxanes, vinca alkaloids) * **Central toxicity** - ifosfamide induced encephalopathy, 5-FU induced cerebellar toxicity * **Ototoxicity** (e.g. pernament cochlear damage with cisplatin)

Question 30

What are the immediate genitourinary SEs of chemotherapy?

Answer 30

* **Nephrotoxicity** - e.g. cisplatin, ifosfamide - renally excreted ∴ adequate renal func required * **Bladder toxicities** e.g. cyclophosphamide, ifosfamide - haemorrhagic cystitis

Question 31

What are the immediate cardiac SEs of chemotherapy?

Answer 31

* **Arrythmias** e.g. doxorubicin, paclitaxel * **Cardiac ischamia** (coronary art spasm) - 5-FU

Question 32

What are the immediate hepatic SEs of chemotherapy?

Answer 32

* ↑LFTs (transient) * Failure (rare)

Question 33

What are the immediate skin and soft tissue SEs of chemotherapy?

Answer 33

* **Extraversion (leakage of IV drugs)** - some chemo = highly vesicant and can cause dmg ∴adminsiter through fast running drips, use dilutants and withdraw if EV occurs * **Palmar plantar erythema (Hand foot syndrome) - temporary** * **​** 5FU, caecitabine, some targetted agents. * Cause unknown. * Tx with emollients. * **Photosensitivity** - 5FU, use high factor sunscreen * **Skin/nail Pigmentation** - beau lines - bleomycin (+ pilmonary fibrosis)

Question 34

What are the 'other' immediate SEs of chemotherapy?

Answer 34

* **Myalgia and arthralgia** - paclitaxel (Tx with NSAIDs) * **Allergic reactions** - paclitaxel and docetaxel ass with hypersensitivity * **\*\*Lethargy\*\*** - general malaise = common and debilitating. Unknown aetiology

Question 35

What are the long term complications with chemotherapy?

Answer 35

* **Secondary malignancies** - e.g. alkylating agents/procarbazine * Sub -lethal DNA dmg → genetic changes → 2^o malignancy * ↓**Fertility** e.g. alkylating agents, high dose * consider sperm/ova storage * **Pulmonary** **fibrosis/pneumonitis** * e.g. bleomycin, busulphan, alkylating agents - particularly high dose/prolonged * **Cardiac fibrosis** e.g. docorubicin * **Psychological and social -** ↓QoL

Question 36

What is the Tx of anaemia?

Answer 36

* Hb \<10gdl - impair quality of life * **Transfusion** * **Recombinant EPO** - ↓risk of transfusion reaction/viral transmission

Question 37

What are the signs of thrombocytopenia?

Answer 37

* Petechial haemorrhage * Nose bleeds * Corneal haemorrhage * Haematuria

Question 38

What is the Tx for thrombocytopenia?

Answer 38

* Ass with high dose chemotherapy (as opposed to standard doses) Tx dep on platelet count * **\<10 x 10⁹** - _Urgent platelet transfusion_ * sig risk of spontaneous bleeding e.g. intra-cerebral * **​10 x 10⁹ - 20 x 10⁹ -** supportive platelet tranfusion * \>**20 x 10⁹ -** do not need platelet trans routinely

Question 39

What are the potential SEs of repeated administration of blood products?

Answer 39

* Development of specific anti-bodies to blood cells * failure to ↑platelet counts immediately after transfusion * Reduce development with using single donor donations

Question 40

What are three main types of targetted agent therapies?

Answer 40

1. **MONOCLONAL ANTIBODIES** (end in _-mab_) - IV infused * Trastuzumab (Herceptin) - HER2 receptor * Ipilimumab 2. **TYROSINE KINASE INHIBITORS** (end in _-ib_) - Oral​ * Erlotinib - anti EGFR for NSCLC * sunitinib - anti-VEGFR (palliative for renal cell, pancreatic, GI stromal) * Vemurafenib - metastatic melanoma * Metabolised by CYP450 - remember drug interactions 3. **mTor INHIBITORS** (end in _-us_) - oral (Everolimus) or IV (temsirolimus) * Serine/threonine kinase inhibitor of mTor, part of the apoptosis pathway. * Palliative in renal cell and in mets breast cancer ER+HER2+.

Question 41

What are the SEs the targetted chemo therapies?

Answer 41

* Theoretically better than normal chemotherapy * More toxic to cancer * Less damage to normal cells * Better tolerated - long periods with fewer breaks (chronic dosing) * However, chronic dosing can lead to: * **Chronic toxicity** - low grade Sx e.g. mild diarrhoea, taste change, rash * tolerable for few weeks but can adversely affect QoL long term * **Emergent toxicity** - only apparent after months of Tx e.g. thyroid disturbance with sunitinib * **Risk of drug interaction** * **Mounting costs**

Question 42

What type of cancers are hormonal therapies useful in?

Answer 42

Only work in cancers which are 'hormone dependent' i.e. cancers arising from tissues under hormonal control * **Prostate** * **Breast** * **Endometrium** * **Lymphocytic** e.g. lymphoma, leukaemia, myeloma

Question 43

At what stages are hormone treatments useful in cancer treatment?

Answer 43

* Shrink 1^o tumours before (**NEOADJUVANT**) OR instead of sugery (**1^o medical therapy**) * Prevent/delay growth of micromets following surgery (**ADJUVANT**) * Shrink estalbished mets and improve QoL/prolong survival (**PALLIATIVE**)

Question 44

Regarding hormone therapies, what techniques are employed to remove SOURCES of hormone production?

Answer 44

* **Surgically** e.g. oophorectomy, bilateral orchidectomy * **Radiotherapy induced ablation** * **Reversible Medical castration**

Question 45

What are the reversible medical castration methods that are used? Name examples for both

Answer 45

**LHRH/GnRH blockers** e.g. goserelin (zoladex), leuprorelin, degarelix (♂) * Block LH/FSH production by pituritary gland (indirectly/directly) (non-menopausal ♀/♂) * ∴ ↓ gonadal hormone production * Not for post-menopausal ♀ ► oestrogen = extra-gonadal (fat/adrenals) **AROMOTASE INHIBITORs** e.g. anastrozole, exemestane, letrozole * Post-menopausal ♀ * Blocks aromatase - converts androstenedione to oestrone * ↓ oestrogen synthesis from androgens

Question 46

How do aromotase inhibitors work?

Answer 46

* **Blocks Aromotase -** Enzyme which aromatases androstenedione (from adrenals) to oestrone (oestrogen synthesis)

Question 47

Why did older versions of aromatase inhibitors require co-prescribed corticosteroids?

Answer 47

* Earlier ones (e.g. aminoglutethimide) used to block earlier stages of steroid synthesis ∴ required corticosteroid supplements. * Newer inhibitors e.g. anastrozole, exemestane, letrozole = more specific blockage

Question 48

Regarding hormone therapies, what methods are used to inhibit hormones?

Answer 48

* Block hormone binding in tumour cell receptors * **Anti-oestrogen -** blocks oestrogen receptors e.g. Tamoxifen (breast cancer) * **Anti-androgen -** blocks androgen receptor (tumour and hypothalamus) e.g. Flutamide, bicalutamide, cyproterone acetate

Question 49

What are the side effects of using LHRH/GnRH blockers and hormone blockers?

Answer 49

* Rapid increase in gonadotrophins ('**FLARE**') (7-10 days) * Can worsen Sx short term e.g. bone pain * **Non specific Sx** * Fatigue * Impotence * Hot flushes/Sweating * Menopausal Sx - vaginal dryness, hot flushes, sweating, ↓labido * Breast tenderness/gynaecomastia * Hair thinning (♀) * Mood changes * ↓Memory * Oesteoperosis (↓testosterone/oestrogen) * ↑weight ∴ ↑cardiac risk * Thrombosis (♀) - esp tamoxifen

Question 50

How could you increase the response of hormone therapy in different cancers?

Answer 50

Combination hormone therapy * Some can produce improved response rates (LHRH blockers + hormone blockers) * However, can ↑SEs without increasing efficacy

Question 51

Regarding hormone therapies, what methods are used to increase hormones? (i.e. tumour growth reducing)

Answer 51

* **Glucocorticoids** - induce apoptosis in malignant lymphoid cells * e.g. lymphoid leukaemia, lymphoma, myeloma, Hodgkin's * **Sex-hormones** to induce -ve feedback loops * oestrogen - down-regulate LRHR in prostate cancer * **Progestogens e.g. medroxyprogesterone acetate** * ​progesterone sensitive tissues (breast, endometrium) * ↓tumour growth by inhibiting progesterone receptor and inducing -ve feedback loops

Question 52

What is radiotherapy?

Answer 52

* Use of ionising radiation for managing loco-regional cance

Question 53

What is the mechanism by which RT works?

Answer 53

* X-rays penetrate body tissue whilst sparing overlying skin * Produce electrons/free radicals that damage DNA in cancers/normal cells * **Normal cells** - repair DNA damage and ∴ survive ('skin sparing') * **Cancer cells** - defective DNA repair ∴ mitotic/apoptotic cell death

Question 54

At what stages in cancer can radiotherapy be used?

Answer 54

* **Radical/curative** - if _no METs,_ may be delivered as sole Tx modality (e.g. prostate cancer) or in combo with chemo * **Neo-adjuvant -** reduce risk of local recurrence e.g. rectal ca * **Adjuvant** - reduce local-regional recurrence e.g. breast Ca * **Palliative** - ↓Sx/↓growth

Question 55

What ways is radiotherapy delivered?

Answer 55

Delivered by LINEAR ACCELERATOR in form of: * Photons/X-rays (External beam)\*\* * Electrons * Radio-isotopes * Protons \*\* most common in UK

Question 56

What units are used to express doses of radiation delivered to body tissues?

Answer 56

Gray (Gy)

Question 57

How is radiotherapy delivered (doses)?

Answer 57

* Series of small doses (fractions) rather than one large dose * Number of fractions and dose (Gy) depends on Tx intent

Question 58

If the intent of RT is curative, what dose/number of fractions would you expect?

Answer 58

* Large dose overall over multiple small fractions * e.g. head/neck - 70Gy in 35 fractions over 7 weeks

Question 59

If the intent of RT is palliative, what dose/number of fractions would you expect?

Answer 59

* Alleviate Sx - small number of fractions and lower doses * e.g. 8Gy in 1 fraction, 20Gy in 5 fractions, 30Gy in 10 fractions

Question 60

Regarding tumour kill and toxicity of RT, what factors can influence the degree of these?

Answer 60

* **Treatment issues** e.g. Tx dose, total volume Tx, doses per fraction, Tx time * **Co-morbidities** e.g. DM, IBD, smoking * **Cancer radiosensitivity** * **​****HIGHLY SENSITIVE -** Germ cells, Lymphocytes e.g. Hodgkins * **MODERATE SENSITIVIE** - Epithelial cells * **HIGHLY RESISTANT -** CNS cells (e.g. glioblastoma multiform), Connective Tissue cells * **Tumour hypoxia -** hypoxic cells 2-3x less sensitive * **Additional treatments** (concurrent chemo increases radio sensitivity but also increased toxicity)

Question 61

What is the term used to describe the balance between tumour control and SEs of Tx?

Answer 61

Therapeutic index

Question 62

What is the most common external beam radiotherpy used? What is the process?

Answer 62

* 3D conformal radiotherapy - individual tumour mapping to target tumour * tumour shape and size measured with CT * Patient immboilised

Question 64

When measuring CT slices for radiotherapy, what volume do you get?

Answer 64

Gross tumour volume (GTV)

Question 65

Regarding RT, what margin is used to account for potential microscopic spread?

Answer 65

Clinical target volume (CTV)

Question 66

Regarding RT targetting, what margin is used to account for minor daily variations in patient/tumour position?

Answer 66

Planning target volume (PTV)

Question 67

Why is a RT plan created? (i.e. RT accounting for gross tumour, clinical target and planning target volumes)

Answer 67

Allow specific targeting and reduce damage to normal tissue.

Question 68

How is the target of RT defined? (GTV, CTV, PTV)

Answer 68

Question 69

What are the instant SEs of RT?

Answer 69

* Teratogenic - CI in pregnancy * Painless during delivery

Question 70

What are the acute SEs of Radiotherapy?

Answer 70

* Localised Tx ∴ SEs related to anatomical areas of body receiving Tx. Usually after first 5-10 fractions. SEs ↑ during Tx and peak in first few weeks * Due to damage of normal tissue (reversible) REMEMBER - SHORT TERM = INFLAMMATION (-itis) * **Fatigue/weakness** * **Skin** - Erythema ► desquamation (peeling, moist, pain) ► ulceration * **Oral -** erythema, ulceration * **Mucositis**/Oesphagitis * Gastrititis/colitis- **N&V/Diarrhoea** * **Rectum -** tenesmus, mucous discharge, bleeding * **Pneumonitis** - cough, dyspnoea, X-ray changes * **Pericarditis**

Question 71

What are the long term side effects of RT?

Answer 71

* \>3 months after RT (can manifest yrs after) - often irreversible, worsen with time, difficult to manage _REMEMBER - LONG TERM SE = BROADLY FIBROSIS (-osis)_ * **Skin** - skin colour change, atrophy, fibrosis, telangiectasia, * **Oral Mucosa** - Dry mouth (salivary gland irridation) * **GI -** mucosal ulceration, fibrosis/obstruction, necrosis * **CNS -** demyelination effects * **Lung** - fibrosis * **Heart -** cardiomyopathy/conduction blocks * **Infertility/↓labido/impotence** * **Carcinogenic** - (2^o cancer 5-30yrs after exposure) - esp thyroid/breast (e.g. mantle RT) and in childhood/young adulthood

Question 74

What is brachytherapy? What is it used for?

Answer 74

* Radiation Tx where radiation sources = placed within/close to tumour * ↑tumour dose and ↓dose to surrounding tissue * Prostate, gynaecological, oesphageal, neck cancers

Question 75

What are the two types of brachytherapy?

Answer 75

1. **Intracavity** - radioactive material placed INSIDE body cavity e.g. uterus, cervix 2. **Interstitial** - material put into target e.g. prostate

Question 76

What is the problem of brachytherapy?

Answer 76

* Patient will be RADIOACTIVE * advise patient about radiation risk to others

Question 77

What cancer uses radioisotopes in its therapy? What does it entail and what are the associated risks?

Answer 77

* Radioisotopes - unstable chemical element - emits radiation when it decays * Thyroid - iodine I-131 * Specifically taken up and concentrated by thyroid tissue * Emits radiation as it undergoes radioactive decay * Patient = irradiated and risk to others * ∴ must remain in lead room until radiation is low so not to pose a risk to others (~4 days)