Oncology Flashcards
Lung cancer staging for exam - TNM
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
Lung cancer treatment for I as well as, II and IIIA
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
Lung cancer treatment for bulky IIIA and IIIB as well as stage IV
Bulky IIIA and IIIB
- NO surgery»_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
Lung cancer EGFR treatment
- 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
Lung cancer ALK treatment
- 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
Lung cancer ROS 1
- Crizotinib targets ROS 1 (in addition to ALK and MET kinase)
- Objective response rate 72%, median PFS 19.2 months
- Entrecitinib - current standard
Lung cancer MET exon 14 mutation
Tepotinib = oral targeted therapy with response rate of 56%, peripheral edema as main SE
Lung cancer and PDL1
High PDL1
- single agent with pembrolizumab
- in combo with chemo Pembroke is effective regardless of PDL1 status
Low PDL1
- combine with chemo
Small cell lung cancer - characteristics (5), treatment (3)
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
Mesothelioma
Pleural malignancy related to asbestos
1st line = ipilimumab and nivolumab or chemo
Median survival 18 months
Upper GI cancer diagnostic workup
- Endoscopy - makes primary diagnosis
- EUS for depth in T-staging
- CT CAP - distant spread
- PET - mets
- Laparoscopy - peritoneal disease
Oesophageal cancer treatment - stage I vs II/III
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
Gastric cancer management - IA, IB-III, and palliative
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)
Zolbetuximab
mab targeting Claudin 18.2 - tight junction protein only expressed in gastric mucosa
survival benefit in metastatic gastric or GOJ (SPOTLIGHT trial)
Drivers of poor prognosis (3) in pancreatic cancer and treatment
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)
Olaparib
selective inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes
effective in cancers with BRCA associated DNA repair defect
TWO hits
Billiary cancer - subtype, presentation, risk factors (5), treatment
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
Prostate cancer screening recommendations
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
androgen deprivation therapy in prostate cancer
refractory within 18-24 months
GnRH antagonist - quicker onset (degarelix)
GnRH agonist - initial stimulation leading to flare > increased pain, precipitate spinal cord compression»_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
prostate cancer chemotherapy = texanes
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
anti-androgens in prostate cancer
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
Bone modifying agents in prostate cancer
> 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
PSMA
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
DNA repair defects in prostate cancer
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
Testicular cancer prognosis
- Morphology - seminoma v non
- Primary site
- Non-pulmonary visceral metastases
- Tumor marker levels (aFP, BHCG, LDI)
Seminoma testicular cancer markers
aFP is not elevated in pure seminoma
bhcg good for follow-up
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
Colorectal cancer in IBD
UC
- pancolitis 5-15x, screen after 8 years
- left-sided 3x
Crohn’s - consider surveillance if >1/3 involvement
Aspirin in colorectal cancer
Initial studies showed benefit
ASPREE for >70yo demonstrated harm
CAPP2 - decreased risk of cancer with 600mg aspirin in HNPCC (Lynch)
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
Colorectal cancer staging
CT CAP
MRI Rectum
Tumor markers
Colonoscopy + biopsy
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)
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
Surveillance post treatment for CRC
CEA
CT CAP annually for 3 years
Colonoscopy within 12 months
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
Irinotecan in CRC
- Topoisomerase inhibitor
- Metabolised by UGT1A1*28: genetic polymorphisms may increase toxicity
- Side effects: Diarrhoea, anticholinergic effects, myelosuppression, alopecia
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
Treatment of dMMR mCRC
Pembrolizumab - PD1
Combination of ipilimumab + nivolumab even better
Toxicity = autoimmune attack can happen in any tissue
BRAF in mCRC
- 10% of mCRC cases
- poor prognosis (<12 months)
- poor response to chemo
Treatment = Encorafenib (BRAF) + cetuximab (EGFR)
Future in CRC
Circulating tumor DNA - risk stratifies stage 2 disease
dMMR in early stage disease - dostarlimab instead of upfront chemo radiation + surgery
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
Early stage GOJ/ gastric cancer treatment
Perioperative chemo with FLOT
- 5-fluorouracil (and leucovorin), oxaliplatin, docetaxel
- neuropathy, myelosupression, lethargy, mucositis
Metastatic oesophagogastric cancer
Poor prognosis
Can try a range of chemo - fluoropyrimidines, platinum, irinotecan, taxanes, TAS102
HER2 +ve»_space; 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
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
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
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.
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
