Clin Shonc

Question 1

Tumour Lysis
1) Pathophys including sequalae:
2) Broadly differentiated into? Key blood results?

Answer 1

Large volume tumour cell death eith spontaneouly or in response to treatment -> Release of intracellular ions, nucleic acids, proteins and their metabolites into the systemic circulation.

Leads to: metabolic abnormalities such as hyperuricaemia, hyperK, hyperphosphataemia, secondary hypoCa and uraemia, can in turn lead to renal failure, arrhythmias, seizures, neurological sx.

2) Laboratory TLS, Clinical TLS
The presence of 2 or more of: HyperUric acid, HyperK, HyperP04-, HYPO Ca (adjusted)

For clinical note the Cairo-Bishop grading of clinical tumour lysis syndrome

Question 2

Prophylaxis/Mx of tumour Lysis syndrome?

Answer 2

1) Evaluate risk:
High proliferation rate, rapid response to Tx anticipated (chemo or radio sensitive), large volume, HR Cancer (lymphoma e.g Burkitts, SCLC), pre-existing metabolic disturbance.
2) Aggressive Hydration, ideally begin 24Hrs prior to Tx. Aim UO >100ml/msqr/Hr.
3) Allopurinol TDS
4)Consider Rasburicase (converts uric acid to excretable)
5) Close monitoring

Question 3

Describe Child-Pugh class.
Rad onc relevance?

Answer 3

Assesses the severity of liver disease, particularly cirrhosis, using 5clinical and lab factors:
Serum bilirubin,
Serum albumin,
Prothrombin time/INR,
Ascites,
Encephalopathy.
Factors scored (1-3) based on severity, and the total score determines Child-Pugh class (A, B, or C)

Liver SABR if <=7 points = A or very low B

Question 4

In DVT Mx (prophylaxis or haem stable) give the two main classes of drug, a brand name for each, MOA.

What drug if patient has HITs?

Answer 4

Haemodynamically stable.
1) Preferred - Rivaroxaban (e.g Xaralto) - Factor Xa inhibitor. Factor Xa promotes coagulation by binding to factor Va to form the prothrombinase.
Normal dose 20mg.
More kidney friendly (GFR>15), high caution if previous haemorrhagic stroke - prefer LMWH.
2) LMWH - e.g Enoxaparin: Activates Antithrombin which inhibits FactorXa.
Not if GFR<30, Hyper K or thrombocytopenia.
Prophylaxis low risk = 20mg/day
HR = 40mg/day
If patient has HITS:

Selective Factor Xa inhibitor Fondoparinux.

Question 5

Medication Mx of PE.

Answer 5

If Haemstable:
Intervention being considered (thrombolysis or pulmonary embolectomy): LMWH, or UFH until intervention.

No Thrombolysis: Rivaroxaban 15 mg BD for 3 weeks
then 20 mg XARELTO once daily.

Unstable:
High bleeding risk: consider pulmonary embolectomy.
Low bleeding risk: Alteplase.

Question 6

Duration of medicaal Mx PE/DVT

Answer 6

• DVT Provoked limited and distal - do 6 weeks
• PE or Unprovoked = 3 months
• Cancer Related!!! 6 months, consider with LMWH then oral Rivaroxaban,

Question 7

List the late toxicities (Mx where applicable) after definitive Chemo RT for stage 3B cervix cancer:

Answer 7

1) Infertility: preTx counseling ect
2) Gynae: Dryness (estrogen cream), stenosis - dilators/reg intercourse
3) Ovarian failure: Address oseoporotic RFs (smoking, lack of weight bearing exercise), vit D, encourage exercise, consider dxa scan. HRT an option with risks.
4) Proctitis: Improve diet, avoid triggers, lopermide PRN.
5) Cystitis.
6) Pelvic insufficiency #s: vit D, analgesia, physio, consider bone denisty
7) Lymphoedema: stay active, weight loss/avoid obesity, lymphoedema practitioner - compression garmets.
8) 2nd maligancy - increased surveillance, lower threshold for Ix.

Question 8

Give grades for urinary toxicity (e.g. after bladder RT):

Answer 8

Grade 0: No toxicity.
Grade 1: Mild symptoms, no intervention needed.
Grade 2: Moderate symptoms, requiring minor or local intervention.
Grade 3: Severe symptoms, requiring hospitalization or significant intervention.
Grade 4: Life-threatening toxicity, requiring urgent intervention.
Grade 5: Death

Question 9

Treatment for paraneoplastic cushings syndrome and most common cause.

Answer 9

SCLC followed by other carcinoid tumours.

1) Treat the tumour
2) Ketoconazole to inhibit cortisol production
3) Octreotide to inhibit ACTH

4) Monitor treat HTN, keep an eye on electrolytes.

Question 10

Give the complete list of Sx and signs associated with an anterior or superior mediastinum mass

Answer 10

Respiratory:
Cough
Dyspnea
Stridor
Orthopnea

Esophageal:
Dysphagia

Nervous:
Hoarseness: due to pressure on recurrent laryngeal nerve.
Pain

Systemic:
Facial and arm oedema due to SVC obstruction
Hypotension
If lymphoma then +/- B Sx

Signs:
Pemberton’s sign
Hamman’s sign = mediastinal crunch or during auscultation over the cardiac apex and left sternal border, synchronous with the heartbeat.

Question 11

Diagnostic criteria for delerium:

Answer 11

The CAM diagnostic algorithm evaluates four key features of delirium:
1) Acute Change in Mental Status with Fluctuating Course,
2) Inattention,
3) Disorganized Thinking
4) Altered Level of Consciousness.

Question 12

Outline you Mx approach to Delerium

Answer 12

(ask the house officer to get a med consult)

1) Confirm Dx (i.e. CAM algor)
2) Investigate and Address cause: iatrogenic, drug withdrawal (via medication review - may need serum drug levels), infection (systems review and septic screening), seizures (Examination ?focal neuro), progression (e.g. lepto on MRI).
3) Safe supportive environment:
- Calm quiet
- Hydration and nutrition needs met
- re-orientation support
- Observatio ect
4) Medical - if above measures insufficient:
- Haloperidol > midaz
- If drug withdrawal diazepam, dose matched with withdrawal scale protocol
- Atypical antipsychotics - in special situations (e.g. Parkinson’s).

Question 13

Rationale and possible MOA for the concurrent use of immunotherapy with radiation

Answer 13

1. Radiation-induced immunogenicity:

a. Radiation damages cancer cells, leading to the release of tumor-associated antigens stimulating immune system not just at tumour site (abscopal effect).

b. Increase the expression of surface antigens on tumor cells, making them more targetable by immune cells.

c. Alter tumour immune microenvironment (TIME) through local release of inflammatory mediators. Can increase number of tumour inflitrating lymphocytes,

2. Immune checkpoint blockade:

ICIs, like PD-1/PD-L1 inhibitors, prevent immune cells from being inhibited by tumor-induced signals, allowing T cells to attack cancer cells more effectively.

3. Synergistic immune response:
   Radiation-induced immunogenicity and ICIs working together can enhance T-cell recruitment to the tumor site.
   More activated T-cell + less inhibition of cell kill via (PD-L1/CTLA) = enhanced cell kill both at the site of radiation but also distally due to pro-inflammatory systemic response post radiation.

Question 14

Side effects of Bevicuzumab?

Benefit in GBM

Answer 14

Improves PFS, no OS benefit, increased tox including grade III events. Controversy around sponsorship by pharmaceutical company.

MOst consequential (due to binding/inactivating VEGF):
GI haemorrhage
GI perforation.

Common:
HTN
Protein urea
Gi Upset

Question 15

What is the CODEL study? What has it found so far?

Answer 15

CODEL: phase III RCT: RT, RT + TMZ, or TMZ for newly diagnosed 1p/19q codeleted oligodendroglioma.(useful for rembering the options for oligo).

Early data shows much less PFS in TMZ alone group

Question 16

Criteria for a test to be used as a screening test:

Answer 16

1) Disease is a significant health problem: Burden to patient/health system/society. WHERE early detection caries benefit.
2) Accuracy - sens/spec
3) efficiency: Cost, accessible
4) Acceptable
5) Treatment available
6) Evidence of screening effectiveness = favourable benefit harm ratio, reduced morbidity/mortality
7) Practical considerations: Can be delivered in health system, ethical (informed consent).

Question 17

Toxicities of immune-checkpoint inhibitors

Answer 17

Most common:
Skin reactions most common: rash, puritis.
GI: diarrhoea, colitis
Endocrine: Thyroid most common - hypothyroidism in particular.

Life threatening: infusion reaction

Other:
Auto-immune:
1) Anti-CTLA-4 inhibitors (e.g., ipilimumab): Rash, pruritus, colitis, and endocrinopathies are frequently reported.
2) Anti-PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab): Hypothyroidism, hyperthyroidism, pneumonitis, and colitis are common
Reactivating radiation pneumonitis
Infusion reaction.

Question 18

Auto immune reactions associated with each class of checkpoint inhibitor:

Answer 18

Anti-CTLA4s, specifically ipilimumab, is more likely to cause immune-related adverse events than other ITs e.g anti-PD1 or anti-PDL1.

Anti-CTLA-4 inhibitors (e.g., ipilimumab):
Rash, pruritus, colitis, and endocrinopathies are frequently reported.

Anti-PD-1/PD-L1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab):
Hypothyroidism, hyperthyroidism, pneumonitis, and colitis are common

Question 19

Signs Sx of depression

Answer 19

1. Intending to sit the phase II exam

A SAD FADS
Anorexia
Sleep disturbance
Attention focus/difficulty
Depressed mood or aggitation
Feelings of guilt/worry/low esteem
Anhedonia
Dysphoria
Suicidal ideation

Question 20

Risk factors for suicide?

Answer 20

SAD PERSONS

Sex = M
Age: younger than 19, older than 45
Depression

Previous attempt
Ethanol/Drug Abuse
Rtionale thinking loss
Separated, single or socially isolated
Organised plan
No social support
Sickness

Question 21

Common NSCLC concurrent chemo?

Who can get durvalumab?

Answer 21

Common:

o Weekly Cisplatin (50mg/m2 D1) + Q4W Etoposide (50mg/m2 D1-5, and D29-33)

o Weekly Carboplatin (2AUC) and weekly Paclitaxel (45mg/m2)

Duvalumab:
Stg 3, TPS>1% any response to ChemoRT and

Question 22

RFs for radiation pneumonitis

Answer 22

Total lung volume irradiated,
Dose (much lass than volume i.e. low incidence SABR)
Tumour size and location (Higher risk mid lower lung), the use of chemotherapy (particularly taxanes), pulmonary dysfunction prior to RT
Age ≥ 70
Concurrent chemo: especially Taxes.
PD-1/PD-L1 inhibitors - reactivating pneumonitis.

Mx:
20-40mg Pred OD for 2 weeks then down titrate based on Sx.

Question 23

Pathophys of radiation induced Xerostomia

Answer 23

1) Ductal epithelial injury -> obstruction
2) Acinar atrophy (these cells highly sensitive to RT): reduced production.

Remember symptomatic Xero can result from:
Change in constituents of saliva
&/or
Decreased production/flow.

Question 24

Mx approach to Xerostomia

Answer 24

Prevention - quit smoking/EtOH, spare salivary glands on plan where possible.

Cytoprotection - Low quality evidence for amiphostine (but has side effects including nausea)

Harm minimise: Oral hygeine and dental review.

Sx Mx:
Cochran review doses not show significant long-term benefit to any intervention (i.e. beyond short term Sx relief)

• Simple Bicarb and sodium MW
• Oral gels and sprays
• Losengers

Some limited evidence that acupuncture can improve salivation after RT.

Question 25

What are the general principles of SABR:

Answer 25

1) Dose – high ablative dose, with dose intensification 125-145% PD, and rapid dose drop off beyond PTV. 2) Immobilisation – requires robust immobilisation and respiratory motion control 3) Motion Mx: dampening with abdominal compression and active breathing control ABC, Gating – tracking tumour’s range of motion during respiratory cycle, and beam switched on only during specific segment of each cycle o Tracking – moving the radiation beam in a near real-time fashion based on respiratory motion using surrogate markers e.g. fiducials - Target volume – tight GTV to PTV expansion - Prescription/ plan review – PTV D98>100%; Dmax< 140% prescribed dose in PTV; CI- 100~1.2-1.3; CI-50<5 3) On treatment image guidance - with pre-treatment +/- mid-treatment verification with 4D CBCT

Question 26

Define "Quality of Life"

Answer 26

WHO defines as: QOL is ‘an individual’s perception of their position in life in the context of culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns’ Definitions vary and objective measurement is limited. Spans multiple domains: e.g. health, material comforts, personal safety, relationship, learning, creative expression, opportunity to help and encourages others, participate in public affairs, socializing, leisure

Question 27

Define "Health Related QoL":

Answer 27

While definitions vary and utility/benefit of a specific definition has been debated, HRQoL refers to the impact of health on a persons perceived QoL. Its measurement usually encompasses at least the below 4 domains: Functional (sometimes objectively assed with ADL measure) Physical Social Psychological

Question 28

For specific HRQoL assessment tools, Name: A general tool a general oncology tool and 2 cancer specific tools.

Answer 28

General: EQD5 - ADLS (basic and independence, mobility), activities, pain, anx/depress. Oncologic: EORTC-QLC-C30 - mulitple domains covered in 30 questions. Boob: EROTC-QLQ-BR Prostate: EPIC Fuck this for a brain dead exercise.

Question 29

Define the following: Absolute Risk Reduction (ARR) Number needed to treat (NNT) Relative Risk (RR) Relative Risk Reduction (RRR)

Answer 29

ARR = I Experimental event rate - Control event rate I NNT = 1/ARR RR = Experimental Event rate/Control Event Rate RRR = ARR/Control event rate = 1-RR

Question 30

Give the Levels of Evidence:

Answer 30

Level 1 – Evidence obtained from systematic review of all RCTs and RCT Level 2 – Evidence obtained from systematic review of cohort studies and cohort studies Level 3 – Evidence obtained from systemiatic review of non-randomized trials case control. Level 4 - Case series Level 5 – Expert opinion/committees

Question 31

The current systemic approach to BRAF+ metastatic melanoma: Outcomes? BRAF neg?

Answer 31

Dual targeting of the tyrosine growth/profliferation pathway (RAS-RAF-Mek-Erk) with molecular therapy at BRAF (Debrafinib) and Mek (Tramekinib) is currently standard and associated with 5yr 0S 55% Dual checkpoint blockade at CTLA and PD1 - 5yr OS 45%

Question 32

Infertility radiation dose:

Answer 32

Ladies: 12Gy (near menarche) to 2Gy (near menopause) Dudes: 6Gy (almost the midpoint between the above range) Hypogonadism from 10Gy

Question 33

You have a long-term patient on the ward, they're looking a bit bumed out. Name and briefly fucken describe an assessment tool you (really the house officer) could use (23.4 marks):

Answer 33

HADS Hospital anxiety and depression scales: 7 questions scored 1-3 on each of: Depression Anxiety with a separate score /21 for each.

Question 34

Define QALY

Answer 34

Common measure in Health Economics, with increasing use in medical research: Years of life GAINED by intervention scaled (i.e multiplied by a number on the interval [0,1]) by QoL score where 0=dead, and 1 = high on acid in Pompey ("Cacator cave malum!"). Its compliment is the DALY - years life lost to a disease, scaled by the shit time you had while sick.

Question 35

Define DALY

Answer 35

Compiment to QALY: Years life losst to disease * (number of years with disease*some weight describing the average amount of disability associated with the disease).

Question 36

Because the college thinks regurgitating lists is important, list the NHMRC levels of evidence: Give multiple examples (where possible)

Answer 36

1: systematic review of RCT trails 2: At least 1 RCT trial 3: Case controlled, case-control series, cohort, comparitive study. 4: Case series 5: Case report, expert opinion, consensus document.

Question 37

What level of evidence is a Case-control series study? Also define and give pro and cons

Answer 37

Level 3: along with cohort,comparitive. And unlike case series (level 4) which isnt controlled. Observational reterospective study commonly used to look at factors associated with diseases or outcomes. 1. Define a group of cases, which are the individuals who have the outcome of interest. 2. Construct a 2nd group "Controls"controls, who are similar to grp 1 but do not have the outcome of interest. 3. Find historical factors to identify if some exposure(s) is/are found more commonly in the cases than the controls. 4. If the exposure is found more commonly in the cases than in the controls, the researcher can hypothesize that the exposure may be linked to the outcome of interest. Pros: not resource intensive, "real world" may have direct relationship with a actual clinical population - rather than a refined population in an RCT. Cons: Confounders not controlled - lack internal validity/or at least estimates of such. Prone to bias - no masking, randomisation, incomplete records.

Question 38

Define basket trial: Give an example:

Answer 38

Tests the effectiveness of a new intervention in patients who have DIFFeRENT diseases that share THE SAME mutation or biomarker. The basket trial offers treatment that targets this specific mutation or biomarker. NCI-MATCH Trial: solid tumours and lymphomas with BRAFV600E mutation targeted with Dab-Tram

Question 39

Define Umbrella trial: Give an example:

Answer 39

In contrast to basket trials, umbrella trials focus on a SINGLE type of cancer but test multiple treatments based on specific genetic alterations. E.g Lung-MAP trial: advanced NSCLC patients divded into subgroups based on actionable mutations.

Question 40

For "non-inferiority trial": 1) Rationale 2) Essential components 3) Appraisal of quality

Answer 40

1) Where a standard treatment has be shown to be better than placebo, and a new treatment offers potential benefits in terms of toxicity/acceptability/cost. The hypothesis tested is that new treatment is not worse (by a predefined non-inferiority margin) - i.e. a onetail test (implies not 2 tail such as superiority/equivalence). 2) Essential components: - New intervention vs standard - Predefined and valid (based on all available superiority evidence) Non-inferiority margin. 3) Appraisal: - Valid objective, i.e is it testing against a current standard. - Ethical: Large a-priori risk/gigh uncertainty whether new intervention prevents access to std of care in intervention group. - Non-inferiority margin reflects all available superiority data and referenced to meta-analysis. - Large sample size- non-inferiority margin is usually small and therefore needs high N - Effect diluted by ITT, needs cross validation with per protocol analysis.

Question 41

What is attrition bias?

Answer 41

Attrition bias is the selective dropout of some participants who systematically differ from those who remain in the study.

Question 42

Observational Population based study: Definition Basic Premise Pros and Cons

Answer 42

In observational studies the exposure is not randomly distributed in a population. The investigator observes the exposure rather than selects the exposure status of an individual. Types of observational studies include cross-sectional, case-control, and cohort. While internal validity (confounders) not controlled, these studies allow insights into "real world" settings and provide insights into genralisability (External validity). It has been argued they can be complimentary to RCT where high internal validity may impair external validity (e.g. by using highly selected clinical groups). Pros: Can be "real world" less restrictive entry than clinical trial - and have good external validity. Less resource intensive than RCT. Can be comlimentary to RCTs. Cons: Confounders are not controlled, cannot control variables of interest.

Question 43

Pros and cons of RCTs

Answer 43

Pros - well designed RCTs can have high degrees of internal validity (confounders controlled) allowing manipulation and isolation of the variable(s)/treatment(s) of interest. Offering objective descriptions of an intervention in terms of clinically/pt relevant endpoints such as OS, disease specific survival, QoL ect. Cons: The cost of high internal validity is often highly selected participant groups (less than 10% of people with a cancer Dx are enrolled in clinical trials). There may be an ensuing decrease in generalisability and external validity. Practical: barriers such as limited institutional resources, burden to patients and clinicians, expenses, restrictive criteria may limit their use, and patient access. Over-emphasis on this type of data, and down playing of phase II data - is a badly designed RCT better than a good Phase II study against historic controls? (no).

Question 44

Screening guidelines for CRC? What agent may be used too. reduce risk in at risk individuals?

Answer 44

In baseline risk individuals: From age 50-75: immunochemical FOBT once every 2 yrs. 85% sensitivity, 90%specificity for early CRC. Sensitivit only 50% for advance disease. Benefit = reduction of CRC mortality by 30%. Aspirin is now supported to signficantly reduce risk of CRC.

Question 45

Assessment of a Pt with suspected malig bowel obstruction:

Answer 45

Acute: Non-prokinetic antiemtic (haloperidol), replace fluid deficit. Hx: previous events (and advanced health directive related to presentation). Consider DDx - infective, iatrogenic (drug, surgical complication). Hx consistent w/ BO - obstipation, constipation, N&V. Ex: Distension, percussion, ausc (high pitch, splaches). Bloods: Electrolyte disturbance, lactate, general. CXR -> Abnormal then CT (e.g. for transition point/cause), gen surg review, early pal care input if conservative Mx only.

Question 46

Conservative Mx of malignant bowel obstruction:

Answer 46

Decide if partial or complete. Bowel rest Iv fluids - replace loss and correct electrolytes. Define pathway (conservative only, surgery) NGT only if necessary - if initial Mx fails to adequately control Sx. TPN - rare as requires a defined end point. Medication by S/c or IV. Meds: 1) IV dex - bowel oedema, anti-emetic 2) Anti-emetic: Complete Obstruction do haloperidol (no kinetic activity), under guidance for partial metoclopramide can be given 3) Anti-secretory: Octreotide. Buscopan if COMPLETE. Consider: Gastrgraffin challenge partial obstruction secondary to adehsions.

Question 47

Steps in a Sentinel Node Bx:

Answer 47

1) Peri tumoural injection of tracer (Blue dye, or Beta-emitter or both). Common radioactive emitter is Technitium-99m. 2) Allow tracer migaration through lymphatics. 3) Identify node (typical intra-operative) using gamma-detection/visual inspection. 4) Incision (small) over site. 5) Nodal excision (typically 1-4 nodes). 6) Specimen sent for pathological assessment.

Question 48

For breast cancer define the following in a nodal specimen: - Isolated tumour cells - Micromet - Macromet.

Answer 48

Isolated tumour cells: A small number of tumour cells <0.2mm in total Micromet: 0.2 to 2mm deposit Macro: >2mm

Question 49

For early breast cancer, which patients dont need a SLNBx? Based on what guideline

Answer 49

ASCO (recent update): Post-menopause and age >50 with: Tumour <2cm Grd

Question 50

A bird with T2 cNO breast cancer has pre-op axillary USS which shows suspicious lumps - Bx is negative. What surgery should she get?

Answer 50

ASCO: WLE + SLNBx.

Question 51

Paraneoplastic syndromes are mediated by:

Answer 51

1) Tumour production of signalling molecules (hormones, peptides) 2) Immune cross reactivity between tumour and normal tissue - e.g. Myaethenia-gravis

Question 52

Discuss at a cellular level, how the radiation induces the abscopal effect.

Answer 52

Tumour cell injury from radiation causes an increase in cellular debris both during necrosis and apoptosis. This leads to: -Release (or loss) of various cytokines and hormones, which exert an endocrine effect on other parts of the body. -Induce an immune response, sensitising the immune system to self antigens. These immune cells may then mount an autoimmune response against tissues elsewhere in the body. -The pseudo-abscopal effect is seen in lymphomas, and is thought to be due to cells entering the field during treatment from other parts of the body.

Question 53

Define stg 1 renal cell carcinoma. Give Mx options: How does this differ from stag II and 3?

Answer 53

Disease confined to kidney (<7cm = T1, >7cm=T2) Preferred definitive surgery (nephrectomy or partial neph) followed by surveillance. Not fit - active surveilance very reasonable. - Ablative - E.g Fast Track. Surgery is the key initial treatment right up to stg IV where curative inetent nephrecctomy and metastectomy or cytoreduction are mainstays. Invasion of perineph, veins (III), or N+/invasion beyond Gerota: Surgery -> surveillance, consider trial. If grade IV histo (rhabdo, sarcomatid, extreme pleo) give Pembro.

Question 54

Systemic options for renal cell carcinoma:

Answer 54

Stg II&III with grd IV histo consider pembro (KEYNOTE STUDY). Stg IV: Remeber in stg IV you can have completely resected disease = surveillance. IF Sarcomatid OR Poor prognosis: Ipi/Nivo Favourable: Sunitinib or Pazo

Question 55

A 5ryo is undergoing CSI for medulloblastoma. How do you monitor toxicity?

Answer 55

Weekly bloods for myelosupression - tx w/prophylactic Abx and antifungals. Weekly review: Child may not be able to communicate Sx such as nausea, so close monitoring and examination including for weight loss needed,

Question 56

Some intermediate to low functioning members of the Aspergers community (same people who ruin drinks at a conference) want you to rapidly list all the systemic options for analgesia for a patient with cancer pain. What is your mnemonic so they fuck off and leave you alone (and you dont have to do the exam again)? List the non-pharm interventions:

Answer 56

NAB DOG (also some evidence for Radium-223..) NSAIDS including paracetamol (which is not an NSAID but the mnemonic P NAB DOG sounded odd) Anti-depress - e.g. Amitryptaline Bone directed Dex Opiods Gaba targeted Non-pharm: - Radiation - Psychological - Nerve injection, ablation - Complimentary - Accupuncture

Question 57

In general, what strategies can be used to manage breathlessness in terminal cancer patients? (2 marks)

Answer 57

Pharmacology - Opioid - Sedative agents (midazolam/ benzodiazepam) - Dexamethasone - anti-secretory (hyoscine, atropine, glyco-pyronium bromide) Non- pharmacology - supplemental oxygen - positioning (slight head elevation) - manage secretion (suction) - ascitic tap - pastoral care/ single room

Question 58

Compare the following: Intention to Treat Analysis As Per-Protocol As Treated

Answer 58

ITT:All participants randomised to an arm are analysed together. Regardless of what happened to them (e.g. no treatment, other treatment). Adv: Preserves randmisation. Pragmatic - encompasses real-world. Preserve eequal sample size. Dis: Conservative estimate of effect. Some outcome data will be lacking. APP: Ideally APP=ITT, analysis of only those patients in an arm who actually recieved/completed Tx. Adv: Less conservative than ITT, neded in non-inf and equivalence trials. Dis: Loss of power, and some internal validity (non-random events not evenly distributed). As treated: All participants studied based the treatment they actually recieved - Defeats purpose of randomisation.

Question 59

On a forrest plot describe the axes, shapes and lines, ant key data columns and rows.

Answer 59

X axis: range of effect size, typically centred at 1 (as Odds ratio). YAxis: The studies with overall effect plotted at bottom as a diamond. Boxes: Point estimate, with size of box proportional to strength of weight. Confidence intervals plotted either side. Diamond: The overall effect point estimate with lateral vertices giving range of confidence interval. Columns: Weights: the influence of each included study in the overall metaanalysis. Point estimates and CIs Control event rate and experimental event rate Name of study Data: Test for overall effect not equal to no effect Test for heterogeniety: too much implies studies are not all measuring the same underlying effect. Should =0.

Question 60

Some fart sniffing twat with an arts degree has defined "Wellness" as? They've made up some bullshit "dimensions", what are those? Rather than allocate funds for practical help, it took countless PhDs to decide that the "3 pillars of survivorship care" are

Answer 60

Complete physical, mental and social well- being and not merely the absence of disease or infirmity. Physical Social Psychological Spiritual Lifestyle (a bullshit word invented by bullshit marketing executives in the 1970s): The 3 pillars of survivorship care are: The survivors The community Health Professionals. These should all be engaged in: - Surveillance - Engagement (e.g. motivation). - Collaboration - Advocacy

Question 61

Outline the pathophyiology/anatomical nature of nausea and vomiting: How is this helpful for the exam?

Answer 61

Mediated by the brainstem Nucleus Solitus Tractus (NST), with inputs from: 1) Cortex (e.g. triggers/conditioned responses, anxiety ect) 2) Chemorecptor Trigger Zone: e.g. drugs, cytokines, electrolytes. 3) GIT: e.g. toxins 4) Vestibular system. All mediated by seritonin (5HT-3), achetylcholine, dopamine (e.g Haloperidol dopamine agonist), other 5HT and H1. - I.e giving the mechanism of action of the drugs. If you comine this with Tumour and treatment factors - you should be able to get all the causes when asked to list them.

Question 62

Approach to N&V:

Answer 62

- Consider the multifactorial nature of N&V (inputs to nucleus Solitus Tractus). Non-Pharm: Identify modifiable causes: CNS: smell triggers, pain, anxiety/distress, annorexia. Chemorecpetors: Drugs, changes in drug (e.g. acute cessation of dex), inflammation, toxins. GIT: Constipation, infection, obstruction Vestibular: vertigo, skull base RT. Pharm: End of life - haloperidol 0.5mg-1mg preferred (no kitetic GIT action), less risk adverse events in frail Pts (ecept parkinson's or Long-QT). Antagonists: 5HOndansetron: 4-8mg

Question 63

-Chemo- Cell cycle phase non-specific chemo (CCPNS) classes: Why is it important?

Answer 63

1) SOME Alkylating agents: - cyclophosphamide (nitrogen Mustard) 1.1) Platinum drugs: Cisplatin, carboplatin, oxaliplatin 2) Anti-tumour antibiotics Anthracycline antibiotics: Doxorubicin Epirubicin Current chemotherapy regimens tend to combine CCPS and CCPNS drugs for maximum efficacy and cancer kill potential.

Question 64

-Chemo- Cell cycle phase specific chemo (CCPS) classes:

Answer 64

ANtimetabolites - work in the S Phase: E.g. Methotrexate. S and G2: Topoisomerase II inhibitors (topoisomerases separate strands of DNA. Drugs the ability of the cell to copy DNA): Etoposide G2: - Bleomycin - Etoposide Mitotic inhibitors (plant alkaloids): - Taxanes (i.e stabilise tubules) - Vinca alkaloids: Vinblastine, Vincristine NOTE: Corticosteroids inhibit G1...

Question 65

How is the Tumour proportion score categorised?

Answer 65

"No PD-L1 expression": TPS<1%. This is often considered negative for PD-L1 and may indicate that a patient is not eligible for IT "Low PD-L1 expression": A TPS between 1 to49%. "High PD-L1 expression:: TPS of 50% or greater. Often associated with a higher likelihood of response to certain immunotherapies, particularly in advanced NSCLC.

Question 66

List as many Sx of hyper calcaemia as you can think of, beginning with the most common, then severe:

Answer 66

Common: FACCPP Fatigue Annorexia Constipation Confusion Polydipsia Polyuria Severe: Arrythmias N&V LOC Abdopain.

Question 67

Give doses for main agents used to treat hyperCa: Key factors to watch post delivery of the most potent common agent. What other agents may be considered and when?

Answer 67

NSaline - IV 4-6L over 24hrs. Zoledronic Acid - Renal function - DO NOT give is GFR<35. 8mg IV given over 15mins. Watch for - Acute phase Rxn, Renal failure, HypoCa If CKD/Renal failure consider Denosumab. Consider calcitonin - especially if severe. IF multiple Myeloma of Lymphoma and high dose Dex!!!!

Question 68

Define mild, moderate and severe hypercalcaemia:

Answer 68

In mmol/L Mild 2.6 to 3. Moderate 3 to 3.5 Severe >3.5

Question 69

Key other investigations for hypercalcaemia:

Answer 69

Bloods: 1) Confirm adjusted result (for alb) 2) Thyroid function and PTH 3) other electrolytes - Mg/PO4- 4) Renal function - e.g. CKD/AKI and prior to ZA (i.e.?GFR<35) 5) Serum vitD. Other ECG

Question 70

Pathogenesis of hypercalcaemia of malignancy?

Answer 70

Due to the marked increase in osteoclastic bone resorption and release of calcium from bone also increased renal retention and GI uptake (PTHrP and calcitrol). 3 main mechanisms: 1) Ososteolytic mets -> local release of cytokines including osteoclast activating factors (commonly seen in multiple myeloma) 2) Tumour secretion of parathyroid hormone-related protein (PTHrP) = increased bone resorption and enhances renal retention of Ca (commonly breast, H&N and kidney ca, Lung SCC) 3) tumour production of Calcitrol leading to increased bone resorption and enhanced intestinal calcium absorption as noted in some lymphomas.

Question 71

Hallmarks of cancer.

Answer 71

(1) sustaining proliferative signaling; (2) evading growth suppressors; (3) enabling replicative immortality; (4) activating invasion and metastasis; (5) inducing angiogenesis and (6) resisting cell death. (7) Tumour promoting inflammation (8) Genome instability.

Question 72

Hallmarks of metastasis:

Answer 72

It is unclear if this is the same magic list as their magic list (multiple lists exist). You are clearly dumb and they are clearly smart for knowing the right list. The below is the most common: I’M PC 1) Invasion and Motility 2) Microenvironment modulation 3) Plasticity - allows adaptation 4) Colonisation

Question 73

Patient factors that influence risk of radiation induced maligancy: Outline the risk over time Outline relationship between dose and risk:

Answer 73

Age: Atomic bomb survior data shows Leukemia risk is near-quadratic response; increased in the early period after bombing then decreased, whereas other solid cancers followed a linear manner; continuing to increase as the cohort ages. Genetic Predisposition/conditions Immunesupression Smoking and other lifestyle choices Environmental exposures. Dose: Essentially linear increase (LNT model) with dose. Bomb survior data again.

Question 74

Current approach to Iodine refractory Papillary or Follicular thyroid cancer:

Answer 74

Metastatic typical treatment is Levatinib - phase III against placebo, very large benefit. But Re-Differentiation therapy (restoration of tumoural 131I uptake) is common, though only limited data. This approach exploits the TKI pathway mutations common to PTC (Braf V600e in 50% - Debrafinib) and Follicular (NRAS/HRAS - Drabatinib). Consider enrollment in the I 1st trial

Question 75

3 key features of immune evasion:

Answer 75

1) Target loss - loss of TAA and TSA antigens. 2) Immune checkpoint inhibition 3) Tumour Immune Microenvironment

Question 76

What is the purpose of a geriatric screening tool? Name 2 (one general, one cancer specific). Uggggghh h h h h h

Answer 76

Identify frail/vulnerable patients who may benefit fro a comprehensive geriatric assessment (GCA). It should be short, sensitive and specific. In oncology EVIQ likes the G8 (elderly cancer patients who could benefit from GCA): 8 things - appetite, weightloss, BMI, depression/dementia, more than 3 meds, pt's perceived health status, Age. Timed up and go: Stand, walk 3M, turn around, walk back and sit, >13 = increased risk falls >20 = predict reduced OS, much increased post op complications.

Question 77

What is the purpose of a comprehensive geriatric assessment (GCA). What should they cover?

Answer 77

To identify factors important to wellness, and treatment outcomes that may be missed by simple clinical assessment. Have been described as "holistic" evaluations. Domains (the 1st 4 or the domains of HR QoL): - Physical: Co-morbs, polypharmcy, frequent hospitalisations ect. - Functional: Timed up and go/falls risk ect, ADLS. - Psychological and cognitive: depression, cog impairment - Social - supports. - Nutritional - Presence of a geriatric syndrome: abuse/neglect, incontinence, dementia ect.

Question 78

Challenges of treating old people

Answer 78

1) Diagnosis: Late presentation with more advanced disease more common, higher-risk delayed diagnosis. 2) Increased risk of toxicity from treatment 3) Difficulty predicting benefit of treatment -e.g. co-morbidities limiting OS (data consistently shows physicians overestimate survival). 4) Failure to appreciate significance of co-morbidities - related to above point, underscores value of screening tools like G8. 5) Expectation balance: Family versus Patient, Both versus reality of increased risks and reduced benefit.

Question 79

Define neutropenic fever:

Answer 79

Patients with a temperature of 38.0°C or higher and neutrophil count of less than 0.5 x 109 cells/L, or less than 1.0 x 109 cells/L and predicted to fall to lower than 0.5 x 109 cells/L.

Question 80

Key goal of Ix and Mx of Neutropenic Fever

Answer 80

Identify and treat within 30min of presentation (delay associated with morbidity and mortality).

Question 81

Approach to Ix and Mx of neutropenic fever

Answer 81

Septic workup. Don’t wait for results. All pts presenting w/fever having anticancer therapy should be mx as neutropenic, and have empiric abx until proven otherwise. Mx may be subsequently modified if nphil count and function are NAD. If no systemic compromise PipTaz 4.5g QID (penicillin allergy then mero 1g tds). If systemic compromise then ADD Gent titrated to renal function.

Question 82

Define cancer cachexia:

Answer 82

Complex metabolic syndrome characterised by: 1) Unintentional weight loss due to loss of muscle bulk and adipose tissue. 2) Chronic systemic inflammation. 3) Anorexia. It arises from: - Tumour induced systemic inflammation. - Negative energy balance: Increased metabolic demand from tumour Decreased intake - Anorexia, N&V, depression, fatigue (often forming functional feedback loops). It is not reversible by nutrition alone.

Question 83

Mx of cancer cachexia

Answer 83

A complex metabolic syndrome (anorexia, negative E balance, systemic inflammation) not reversible by nutrition alone. Non Pharm: Address underlying contributing factors- eg ADL assistance, depression, fatigue. Address nausea and constipation. Nutrition and increased activity. Pharm: 1) Steroids: phase 3 evidence for improved QoL and appetite. 2) Progesterone: phase 3 evidence appetite and weight gain. 3) Ghrelin. Some evidence. Note: Canananoids no better than placebo. Which is interesting, especially if you’ve ever accidentally eaten a whole box of dry cereal….

Question 84

A fit 70yro has been Dx with NSCLC with no PDL expression or actionable mutations. Common systemic options? How about if ECOG2 or “good” 3 (and unrealistic).

Answer 84

Cisplatin + gemcitabine +/- bevacuzumab. ECOG 2 do carbo+gem ECOG1 or 0, With progression could consider nivolumab or Docetaxel

Question 85

Give the mechanisms of action and contraindications for the following: 1) Ondansetron 2) Metoclopramide 3) Prochlorperazine 4) Olanlazipine 5) Haloperidol 6) Cyclizine

Answer 85

1) Ondansetron: 5HT3 antagonist - recptor both at vagal nerve and chemotrigger zone (hence may not be very effective for CNS inputs to NST). Also slows gut motility - Contras- long QT syndrome. 2) Metoclopramide: Dopamine receptor antagonist - Increase bowel motility. - Contras: Bowel obstruction, Parkinsons, pheos 3) Prochlorperazine: Same as Metoclopramide = Dopamine antagonist. 4) Olanlazipine: 5HT2 + D2. Pretty well tolerated. 5) Haloperidol: Dopamine D2 antagonist - pretty well tolerated - 1st choice in SBO as no effect on motility 6) Cyclizine - H1 receptor antagonist - mainly used for vertigo. Lots of contras - glaucoma, SBO/risk of SBO, urinary retention, epilepsy

Question 86

Approach to Mx of depression in the oncology setting

Answer 86

30% risk - some phase III evidence for prophylaxis (e.g. escitalopram). Non-pharm: - Identify underlying cancer and cancer-unrelated causes - e.g. improve Sx Mx, identify iatrogenic factors (e.g ADT) Specific resources: 1. Crisis intervention. 2. CBT 3. Social Group. 4. Other: Masssage, substance abuse councilling, recreation fart lighting. Drugz: SSRIs (Escitalopram, sertraline), SNRI (venlafaxine), TCA (Amitriptaline).

Question 87

Define cancer related fatigue:

Answer 87

Persistent subjective experience of physical and/or emotional/cognitive tiredness or exhaustion that arises from cancer or its treatmenmt. It is out of proprtion to recent activity and impacts function.

Question 88

Mx of cancer related fatigue:

Answer 88

1st rule out common cancer causes: Depression, anaemia, polypharmacy/opiods. Non-pharm: - Increase activity: Slowly introduce regular activity such as break dancing, or prolonged elcetrocution. - Improve diet/other lifestyle factors such as huffing glue. - Sleep hygeine - Appropriate rest - maybe they need a holiday. Farm: - Insominia: temaz/melatonin/studying clin onc - Tx pain - tx depression - Tx anaemia - Consider short term dex (you know you have).

Question 89

Your center has unacceptable wait times, what measures could be used to Mx this (besides taking inspiration from Soylent Green):

Answer 89

1. Workflow: Identify and improve bottlenecks. Replace everyone with AI - Pre-planning - E.g delays due to overbooked MDMS (priorites MDMs - e.g. dont discuss every breast fibroadenoma). Issues with inappropriate triage - improve refrral template. - Planning: Increase staff, identify unnecessary planning steps. Palliative Pts - plan on Dx scan. - Treatment: E.g. change to VMAT/new techniques, streamline pt setup. 2. Limited capacity of resources: Increase work force, increase hours. 3. Fractionation: Safe and evidence based approach to adopting lower fraction regimens (e.g. 8Gy) 4. Neoadjuvant Tx pathway. 6. Prioritisination: Well-defined prioritisation guidelines 7. Ask for help - referral to other centers.

Question 90

For a question about meetings - either Peer Review or MDMs. Give essential elements: Give potential problems/barriers: Give benefits (note RCT data does not really show a benefit, but people dont want to know that):

Answer 90

Essential Elements (pad the below headings with bullshit): 1) People: i.e. enough for meeting, multidisicplinary 2) Time 3) Physical resources: i.e for planning software (Peer_, or radiologist (MDM), ability to televideo. 4) Process: - PR: For Pt selection, gathering enough info for discussion (Hx/Dx ect), documentation, allocation of responsibilities if actions required. - MDM: Referral process, discussion format, chairperson ect. 5) Culture: A "Just Culture" that facilitates optimal out comes. Potential Barriers: Luckily its just the above headings - may some shit up for each (e.g. People - everyone has leporsy) "Benefits" 1) Quality assurance has 2 parts: - Ensure standard of care - Identify errors/problems 2) Education 3) Culture

Question 91

What are the purposes of MDMs or Peer reviews?

Answer 91

The purpose/Aim = the "benefits" "Benefits" 1) Quality assurance has 2 parts: - Ensure standard of care - Identify errors/problems 2) Education 3) Culture

Question 92

Causes of increased wait times?

Answer 92

1) Increased demand. 2) Decreased resources 3) Inefficiencies.

Question 93

For Mx of depression and Anxiety, give the 3 key headings when answering such a question.

Answer 93

depression and anxiety in the cancer patient is best managed by a combination of 1) drugs, 2) supportive psychotherapy and 3) cognitive behavioural techniques