Oncology Flashcards
Treatment Mesothelioma
Nivolumab - PD-1 inhibitor
Ipililumab - CTLA4 inhibitor
Not curative, only improves survival by 4 months
Side effect of GnRH Agonist
Early increase in testosterone levels cause progression of bony mets and prostate enlargement - risk of cord compression and urinary retention
Side effect of Abiraterone
Blocks 17-hydroxylase
Increased mineralocorticoid effect
requires co-administration with steroids to reduce mineralocorticoid effect (Hypokalaemia, Hypertension, peripheral oedema)
Hormonal therapy in ER/PR positive women
Pre-menopausal - Tamoxifen
Post-menopausal - Aromatase inhibitors - block androgen conversion to oestrogen (can cause progression in pre-menopausal women)
EGFR mutation in lung cancer
Asian women, non-smokers with adenocarcinoma - treated with EGFR tyrosine kinase inhibitors Rx with Gefitinib and erlotinib
If EGFR T790M resistant, use Osemertinib
T790M resistance mutation of lung cancer
EGFR T790M resistance to EGFR TKI Gefitinib and erlotinib, requires Osemertinib
Mutations in CRC
Germline;
- Lynch Syndrome - DNA mismatch repair (MLH1, MSH2, PMS2, MSH6)
- Familial adenomatous polyposis - adenomatous polyposis gene on chromosome 5
Somatic;
- BRAF - methylation causing DNA mismatch repair - R) sided with poor prognosis
- KRAS
- EGFR (BRAF/KRAS wild type) - L) sided with good prognosis
Aromatase inhibitors
Used in hormone receptor positive breast cancers in post-menopausal women only
Side effect: Osteoporosis, vaginal atrophy
Tamoxifen
selective oestrogen receptor modulator (SERM) for hormone receptor positive breast cancer.
Causes thrombosis, hot flushes, increased risk of endometrial cancer
Should not be used with paroxetine or fluoxetine (CYP inhibition)
Has positive effects on bones and lipid profile
HER2 inhibition
Trastuzumab - can cause cardiotoxicity
Lapatinib - preferred if EF < 45% or known brain mets
Cell cycle
G0 - Quiescent state
Interphase
G1 - protein and cell contents replication, except DNA
S - DNA replication
G2 - Microtubule production
Mitosis - cell division
Cytokinesis
Best tumour marker for monitoring disease
Beta-HcG or AFP in testicular cancer
Treatment of ovarian cancers
- Debulking surgery
- Platinum based chemotherapies with Paclitaxel + Carboplatin
- PARP inhibitor - Olaparib
- Genetic testing for BRCA in all ovarian cancers
Most common renal cell carcinoma
Clear cell due to Von-Hippel Lindau mutation
Originate from Proximal convoluted tubule
Treat with IL-2
Types testicular cancer
Seminoma
- Beta HcG
- Responsive to radiotherapy
Non- Seminoma
- AFP and Beta HcG
- Non-responsive to radiotherapy
Management Testicular cancer
Low risk
- Radical Orchidectomy followed by active surveillance;
1st year monthly., 2nd year 2 monthly, 3rd year 3 monthly, 4th year 6 monthly - Then yearly.
- If patient non-compliant with F/U use Cisplatin Chemo
High Risk
- Radical orchidectomy
- BEP chemotherapy - Bleomycin, Etopocide, cisPlatin
- Radiotherapy for seminoma only
p53
Tumour Supressor Gene - arrests cell cycle in G1 to allow for DNA repair or programmed cell death
If mutated, prevents DNA repair and drives cancer
In B cells - p53/17p deletion drives CLL, Rx Ibrutinib
Mutation associated with clear cell renal cancer
Von Hippal Lindau (VHL)
Side effect of VGEF inhibitors
I.e Bevacizumab in BRAF/KRAS mutant CRC
I.e. Sunitinib in renal cancer
Hypertension
Treatment for prostate cancer
If castrate sensitive - for androgen deprivation therapy
- GnRH agonists (Groselin)-> can flare before improvement
- GnRH antagonists (Degarelix)
If castrate resistant
- Taxel based chemo -> ototoxicity
- 17-hydroxylase inhibition - Abiraterone -> Mineralocorticoid production Rx w Pred
- Androgen receptor antagonist - Enzalutamide
Breast cancer screening
Mammography every 2 years from 50-74 years of age
If BRCA positive, mammography or USS every 2 years from age 25, or 5 years before youngest affected relative
BRCA screening
- Any (Non-mucinous) ovarian cancer Dx < 70 years, or any age if personal or FHx of breast cancer w ovarian cancer
- triple negative breast cancer < 60 years of age
- breast cancer < 40
- Manchester score > 15
- Ashkenazi Jewish population
BRCA treatment
- Platinum base chemotherapy
- PARP inhibitors (Olaparib)
- Salpingoopherectomy
- Contralateral mastectomy
Side effect of Trastuzumab
Cardiotoxicity with reduced LVEF
Mutations associated with NSCLC
EGFR (Gefitinib/erlotinib) > ALK (Alectinib) > ROS1 (Crizotinib)
+/- check for PDL status (Nivolumab/pembrolizmab/Atezolizumab +/- Ipalilumab CTLA4 inhibition)
Types of chemotherapy
Alkalysing agents - inhibit unfolding DNA helix - “Platins”
Anti-metabolites - 5FU (Check DPD), 6-MP (check TPMT)
Alkaloids - inhibit microtubules - Vincristine, Taxels
Topoisomerase inhibitor - etoposide, Anthramcyclins - Bleomycin (from streptomycin), Doxorubicin, cyclophosphamide
Cisplatin side effects
Neuropathy, Ototoxicity, metabolic syndrome and Nausea (most highly emetogenicity)
Lynch Syndrome
Germline mutation in Mismatch repair genes causing Microsatellite instability (MLH1 - highest risk, MSH2, PMS2, MSH6)
BRAF mutant
Autosomal dominant inheritance
BRCA 1 vs 2
BRCA 1 is more common and most likely to be associated with;
- Medullary breast cancers
- Serous ovarian cancer (mucinous ovarian cancer not associated with BRCA)
- Prostate cancer in Men
- Triple negative
BRCA2
- increased risk of breast cancer in males
- hormone receptor positive breast cancer
Chemotherapy for breast cancer
Doxorubicin and cyclophosphamide
Non-chemo treatments for breast cancer
Trastuzumab - HER 2 +
Tamoxifen - SERM - ER/PR + pre and post menopausal
Aromatase inhibitors - PR/ER+ post menopausal
CDK 4/6 - Abemaciclib - PR/ER + metastatic breast cancer
T DM1 - Trastuzumab plus chemotherapy (emtansine/DM1) - HER 2+
GIST tumour
From cells of Cajal
Associated with KIT-C CD117 (same as melanoma)
Spindle cells
FOBT screening
2 yearly over age 55
Bowel cancer screening - Moderate risk
Colonoscopy every 5 years or 10 years before age first affected relative
Bowel cancer screening - Lynch and FAP
Lynch - colonoscopy yearly from 25 or 5 years before first relative
AFP - colonoscopy yearly from age 15
