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Oncology Flashcards

1
Q

Lung cancer staging for exam - TNM

A

T1 3cm
T2 3-5cm, involves visceral pleura or main bronchus in the same lobe
T3 5-7cm, chest wall, pericardium, phrenic nerve or seperate tumour nodule
T4 >7cm, mediastinum, diaphragm, heart, great vessels, recurrent laryngeal nerve, carina, trachea, oesophagus, spine or tumour nodule in ipsilateral lobe

N1: ipsilateral, 2 mediastinal, 3 contralateral

M1a: effusion/nodules/contralateral love, 1b single extra thoracic, 1c multiple

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2
Q

Lung cancer treatment for I as well as, II and IIIA

A

early stage (T1 or T2, N0) - lobectomy + lymph node dissection

II and IIIA
- adjuvant chemotherapy via cisplatin based combination provides modest survival benefit
- immunotherapy: PD-L1 with atezolizumab showed 0.66 DFS and 0.81 OS

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3
Q

Lung cancer treatment for bulky IIIA and IIIB as well as stage IV

A

Bulky IIIA and IIIB
- NO surgery&raquo_space; cisplatin based chemoradiotherapy
- addition of Durvalumab (PDL1) provides HR 0.59
- coming soon: addition of nivolumab HR 0.43

IV
- Non-squamous look for driver mutation: EGFR, ALK, ROS1, RET, KRAS, HER2, MET, NTRK, BRAF
- No driver or Squamous: PDL-1 (high v low)
- ECOG 2 or less

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4
Q

Lung cancer EGFR treatment

A
  • epiregulin and transforming growth factor a receptor (HER1-4)
  • More common in adenocarcinoma, asian, young woman, never smoker
  • 1st gen = Erlotinib, Gefitinib (resistance with T790 mutation)
  • 3rd gen = Osimertinib (current standard - better CNS penetration, less skin toxicity)
  • SE: acneiform rash, diarrhoea, ocular, alopecia, nail, pulmonary
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5
Q

Lung cancer ALK treatment

A
  • ALK - receptor tyrosine kinase (translocation is associated with anapaestic large-cell lymphoma hence ALK)
  • adenocarcinoma, asian, men, never/ light smoker
  • Alectenib (better than crizotinib) - 5 year OS 62.5%
  • SE: visual, neutropenia, altered bowels, pulmonary, fluid retention, hepatotoxicity, bradycardia, prolonged QT, fatigue, cytochrome p450
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6
Q

Lung cancer ROS 1

A
  • Crizotinib targets ROS 1 (in addition to ALK and MET kinase)
  • Objective response rate 72%, median PFS 19.2 months
  • Entrecitinib - current standard
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7
Q

Lung cancer MET exon 14 mutation

A

Tepotinib = oral targeted therapy with response rate of 56%, peripheral edema as main SE

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8
Q

Lung cancer and PDL1

A

High PDL1
- single agent with pembrolizumab
- in combo with chemo Pembroke is effective regardless of PDL1 status

Low PDL1
- combine with chemo

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9
Q

Small cell lung cancer - characteristics (5), treatment (3)

A

Strong smoking association
80% advanced stage at presentation
Chemo sensitive
Paraneoplastic syndromes
CNS metastasis common - MRI brain

1st line = atezolizumab + cisplatin + etoposide
RT for limited stage

Median survival 1 year

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10
Q

Mesothelioma

A

Pleural malignancy related to asbestos

1st line = ipilimumab and nivolumab or chemo

Median survival 18 months

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11
Q

Upper GI cancer diagnostic workup

A
  • Endoscopy - makes primary diagnosis
  • EUS for depth in T-staging
  • CT CAP - distant spread
  • PET - mets
  • Laparoscopy - peritoneal disease
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12
Q

Oesophageal cancer treatment - stage I vs II/III

A

I - resection

II or III
- chemoradiotherapy followed by resection
- adjuvant (post CRT and surg) nivolumab (PDL1) improves DFS 0.69

chemo + nivolumab or pembrolizumab;
trials with doublet immuno > chemo

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13
Q

Gastric cancer management - IA, IB-III, and palliative

A

IA - endoscopic or surgical resection

IB-III
- pre-op chemo or not
- surgery followed by post-op chemo

Palliative
1st line - chemo + PD1 (nivolimumab or pembrolizumab)
- 5FU/capecitabine + cisplatin
- FOLFOX (5FU/capecitabine + oxaliplatin) +/- trastuzumab (HER2 over-expressing - HR 0.74; conjugate with deruxtecan has better outcomes HR 0.59)

2nd line
- Irinotecan
- Paclitaxel +/- ramucirumab (anti-VEGFR2 - minor benefit HR 0.78-0.81 but barely statistical)

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14
Q

Zolbetuximab

A

mab targeting Claudin 18.2 - tight junction protein only expressed in gastric mucosa

survival benefit in metastatic gastric or GOJ (SPOTLIGHT trial)

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15
Q

Drivers of poor prognosis (3) in pancreatic cancer and treatment

A

Vague symptoms leading to late presentation (60% metastatic)

Aggressive biology
Desmoplastic stroma
Low immunogenicity

Surgery if possible, then chemo
- Nab-paclitaxel/gemcitabine
- FOLFIRINOX - 5FU/irinotecan/oxaliplatin (best - high rates of infections)

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16
Q

Olaparib

A

selective inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes
effective in cancers with BRCA associated DNA repair defect
TWO hits

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17
Q

Billiary cancer - subtype, presentation, risk factors (5), treatment

A

Adenocarcinoma most common

Jaundice, weight loss, RUQ pain

Risk = PSC, liver disease, cholelithiasis, obesity, metabolic syndrome

Treatment
- surgery with post capcetibine
- cisplatin-gemcitabine +/- durvalumab (PD-L1 inhibitor)

otherwise targeted
- IDH1 = ivosidenib
- FGFR2 = pemigatinib or infigratinib
- BRAF = dabrafenib-trametinib
- MSI-H/dMMR = pembrolizumab
- HER2/neu = trastuzumab-pertuzumab

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18
Q

Prostate cancer screening recommendations

A

2 yearly PSA for 50-69yo
- outside of these ranges would be individualised to risk

Family Hx: 1st degree 3x risk - start at 45yo
3x 1st degree 10x risk - start at 40yo

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19
Q

androgen deprivation therapy in prostate cancer

A

refractory within 18-24 months

GnRH antagonist - quicker onset (degarelix)

GnRH agonist - initial stimulation leading to flare > increased pain, precipitate spinal cord compression&raquo_space; combine with anti androgen for 2 weeks prior and continue for another 4 weeks (goserelin, leuprorelin)

SE: vasomotor symptoms, reduced libido, bone loss (greater than 4 doses), muscle loss, CVD

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20
Q

prostate cancer chemotherapy = texanes

A

Texanes: docetaxel, carbazitaxel
- interfere with microtubule growth
- survival advantage in castrate resistant
- docetaxel survival advantage as first line in combo with androgen deprivation
- SE: hair loss, N/V, pancytopenia, mucositis/ diarrhoea, lethargy, fluid retention, peripheral neuropathy, hypersensitivity

21
Q

anti-androgens in prostate cancer

A

Previously used in castrate resistant but now first line in combination with androgen deprivation

Abiraterone
- androgen biosynthesis inhibitor (17α-hydroxylase) in the adrenal gland
- testosterone and cortisol levels fall > need steroids
- shunting leads to hyperaldosteronism

Enzalutamide, Apalutamide, Darolutamide
- direct androgen receptor antagonist
- SE: fatigue, cognitive impairments, falls, seizures, rash

22
Q

Bone modifying agents in prostate cancer

A

> 4 doses of ADT carry increased risk of fracture

PBS only covers if osteoporosis or previous fracture or metastatic bony disease - otherwise self-funded

Bisphosphanates - inhibit tumour cell adhesion and disables activated osteoclasts
Denosumab - inhibits activation of osteoclasts

23
Q

PSMA

A

prostate-specific membrane antigen PET scan with galium
- 95% of prostate cancer will over-express
- reimbursed for initial staging of intermediate - high risk prostate Ca
- re-staging of recurrent

Lu-PSMA = therapeutic by delivering lutetium in a targeted manner (very costly)
- overall survival benefit in PSMA-positive metastatic castrate resistant cancer
- next study showed no improvement in OS but better PSA response, radiographic, and PFS

24
Q

DNA repair defects in prostate cancer

A

1/3 will have some defect: BRCA2 (44%), ATM (13%), CHEK2 (12%), BRCA1 (7%)

Target with PARP inhibition (the alternate pathway to DNA repair) - Olaparib

25
Testicular cancer prognosis
1. Morphology - seminoma v non 2. Primary site 3. Non-pulmonary visceral metastases 4. Tumor marker levels (aFP, BHCG, LDI)
26
Seminoma testicular cancer markers
aFP is not elevated in pure seminoma bhcg good for follow-up
27
Testicular cancer treatment
Stage 1 - orchidectomy followed by adjuvant carboplatin for seminoma or BEP for NSCGT Metastatic/ Advanced - BEP - bleomycin, etoposide, cisplatin SE: pancytopenia, alopecia, lethargy, hearing impairment (P), renal impairment, pneumonitis (B) - resection of residual mass(es) Refractory - second line chemo
28
Colorectal cancer in IBD
UC - pancolitis 5-15x, screen after 8 years - left-sided 3x Crohn's - consider surveillance if >1/3 involvement
29
Aspirin in colorectal cancer
Initial studies showed benefit ASPREE for >70yo demonstrated harm CAPP2 - decreased risk of cancer with 600mg aspirin in HNPCC (Lynch)
30
Colorectal screening
50-74yo get 2 yearly immunochemical FOBT Category 1 = 1 relative with cancer >55yo, 2x risk, FOBT from 45yo 2 = 1 first degree <55yo, 2 first degree of any age, 1 first degree and 2 others, 3-6x risk, FOBT 40-50yo then colonoscopy 50-74 3 = 3 relatives with 1 <55yo or 3 first degree, FOBT 35-45 then colonoscopy 45-74
31
Colorectal cancer staging
CT CAP MRI Rectum Tumor markers Colonoscopy + biopsy
31
Colorectal cancer treatment
Surgery Neo adjuvant if T3/4 to downstage Adjuvant if IIA - IIIC - to eradicate micro metastatic disease - stage 2 has modest benefit but consider depending on risk - stage 3 is a clear indication - CAPOX (capecitabine, oxaliplatin) vs FOLFOX (colonic acid, fluorouracil, oxaliplatin)
32
CRC chemotherapy agents
Fluoropyrimidines - 5-fluorouracil or capecitabine - Hand foot syndrome, diarrhoea/ mucositis, myelosupression, rare cardiac - DPD deficiency = increased toxicity Oxaliplatin - Peripheral neuropathy (cumulative), N/V, diarrhoea, lethargy, myelosupression, laryngeal dysaesthesia, hypersensitivity
33
Surveillance post treatment for CRC
CEA CT CAP annually for 3 years Colonoscopy within 12 months
34
Systemic therapy for metastatic CRC
Usually chemo +/- targeted UNLESS dMMR (MSI high) or BRAF mutated second-line Single agent - fluoropyrimidines (5FU or capecitabine); irinotecan; TAS102 Doublet – addition of oxaliplatin (FOLFOX/CAPOX) or irinotecan (FOLFIRI/CAPIRI) to fluoropyrimidine Triplet - 5FU, oxaliplatin and irinotecan - FOLFOXIRI
35
Irinotecan in CRC
- Topoisomerase inhibitor - Metabolised by UGT1A1*28: genetic polymorphisms may increase toxicity - Side effects: Diarrhoea, anticholinergic effects, myelosuppression, alopecia
36
Targeted therapies in metastatic CRC
VEGF inhibitors - bevacizumab - regardless of RAS/RAF status, location - hypertension, poor wound healing, intestinal perforation/ fistula, bleeding, thrombosis EGFR inhibitors - cetuximab/panitumumab - Only in RAS WT tumours, LS primary - resistance with downstream RAS or BRAF activation - acneiform rash, dry skin, fissures, diarrhoea, low Mg, infusion reactions
37
Treatment of dMMR mCRC
Pembrolizumab - PD1 Combination of ipilimumab + nivolumab even better Toxicity = autoimmune attack can happen in any tissue
38
BRAF in mCRC
- 10% of mCRC cases - poor prognosis (<12 months) - poor response to chemo Treatment = Encorafenib (BRAF) + cetuximab (EGFR)
39
Future in CRC
Circulating tumor DNA - risk stratifies stage 2 disease dMMR in early stage disease - dostarlimab instead of upfront chemo radiation + surgery
40
Early stage oesophageal/GOJ cancer treatment
Neoadjuvant “CROSS” chemoradiation - Squamous cello esophagus - Adenocarcinoma oesophagus and GOJ - Chemo backbone – carboplatin/paclitaxel Nivolumab x 12m if no path CR – now on PBS
41
Early stage GOJ/ gastric cancer treatment
Perioperative chemo with FLOT - 5-fluorouracil (and leucovorin), oxaliplatin, docetaxel - neuropathy, myelosupression, lethargy, mucositis
42
Metastatic oesophagogastric cancer
Poor prognosis Can try a range of chemo - fluoropyrimidines, platinum, irinotecan, taxanes, TAS102 HER2 +ve >> Trastuzumab (plus chemo) Nivolumab PBS approved 1st line in combination with platinum-FP chemo for adenoCa + PDL1 +ve oesophageal SqCC Nivolumab PBS approved 2nd line after platinum-FP chemo for oesophageal SqCC
43
Pancreatic cancer treatment; gemcitabine
Early-stage - whipple's Adjuvant (or neo) - FOLFIRINOX Metastatic = poor prognosis - FOLFIRINOX v gemcitabine 11.1 v 6.8 OS Gemcitabine - pyrimidine analog - Pneumonitis - Potent radiation sensitiser
44
Oncology treatment induced diarrhoea - severity, common agents
Moderate 4-6 5 FU, capecitabine, irinotecan, radiation, immunotherapy Treatment (after excluding infection) 1. Rehydration 2. Loperamide - decreased motility via opioid action - diphenoxylate + atropine is an alternative 3. Octreotide - somatostatin analogue that decreases secretion Immunotherapy - treat as IBD
45
46
PD-1 inhibitors enhance anti-tumour activity by: a. Preventing programmed cell death of T cells. b. Enhancing IL-2 release from T cells. c. Preventing autonomous activity of the mTOR pathway. d. Enhancing the ability of APCs to activate T cells. e. Allowing tumours cells to die instead of having DNA damage repaired.
Answer: A PD-1 inhibitors like Nivolumab and Pembrolizumab work by disrupting the binding of PD-1 on T cells to PDL1 on tumour cells. This interaction leads to T cell programmed cell death, so disruption of the interaction allows the T cells to go on, be activated and combat the tumour. Option C describes the action of mTOR inhibitors. Option D describes the action of CTLA4 inhibitors. Option E describes the action of PARP inhibitors.
47
A 57yo male is brought to ED with melena associated with a drop in Haemoglobin of 15g/L. His background includes NSTEMI on Aspirin 100mg mane, CLL on Ibrutinib 420mg daily and Famciclovir 500mg BD, Rheumatoid Arthritis on Hydroxychloroquine and hypertension on Telmisartan/Amlodipine 40/10mg mane. Which of his medications is the most likely cause of his GI haemorrhage? A. Aspirin B. Ibrutinib C. Famciclovir D. Hydroxychloroquine
B Ibrutinib is a BTK inhibitor associated with an antiplatelet effect. In one major study there was a 66% rate of minor bleeding and a 6% rate of major haemorrhage. Other characteristic side effects include AF, Hypertension, GI symptoms (nausea, diarrhoea), neutropaenia, opportunistic infections and headache. Aspirin is associated with bleeding but at a relatively low rate. Hydroxychloroquine is associated with a modest antiplatelet effect which is not clinically significant. Telmisartan and Amlodipine has no bleeding risk associated

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