Oncology

Question 1

What are screening programmes for Breast Ca?
What are screening programmes for CRC?
What are screening programmes for Cervical Ca?

Answer 1

1) Breast: Mammogram = 2 yearly for women aged 50-74
2) CRC: Home FOBT = 2 yearly from age 50
3) Cervical: Pap smear = every 2 years from age 18 to 70

Question 2

Malignancy history - GO!

Answer 2

P: ECOG. 0- asymptomatic. 1- symptomatic but well/active.
2- resting for <50% of waking hours. 3- resting for >50% of waking hours. 4- bedbound. Stage. Prognosis
R: Smoking, FHx
I: Diagnosis- biopsy, imaging. Staging
M: Surgery, Chemotherapy +/- immunotherapy, RT, Symptom management, Palliative care, Follow up- bloods, imaging, screening
C: Pain- NSAIDs (bone pain or inflammatory), glucocorticoid, opioids, gabapentin/pregabalin/duloxetine, bisphos/ denosumab, RT, treat depression; SCC compression- steroid, surgery, radiotherapy; SVC obstruction- endovenous stenting + steroids if symptomatic, chemo +/- RT

Question 3

What are acute and long-term radiotherapy complications?

Answer 3

> Acute
-alopecia, skin erythema, GI (mucositis, nausea/vomiting), cystitis, bone marrow suppression, CNS
Long term
-skin fibrosis, cardiac (fibrosis, cardiomyopathy, coronary artery disease), pulmonary pneumonitis/fibrosis, GI/GU fibrosis, endocrine (infertility, hypothyroidism, panhypopituitarism), neurological (neurocognitive defects if cranial irradiation, myelopathy), secondary malignancy

Question 4

What are the SEs of specific chemo in Lung adenocarcinoma?

Answer 4

> EGFR inhibitors: Erlotinib, gefitinib, afatinib, osimertinib
-Acne, pneumonitis/ILD
ALK inhibitors: Crizotinib, ceritinib, alectinib
-N/V/diarrhoea; hepatotoxicity; pneumonitis
-increased by P450 3A4 inhibitors
PD-1 inhibitors: nivolumab, pembrolizumab, atezolizumab, >and CTLA-4 inhibitors: ipilimumab.
-Induction of autoimmune disease in any organ system (e.g. pneumonitis, hepatitis)
-hypo/hyperthyroidism, colitis, hypophysitis, nervous system (Mx- steroids)

Question 5

What agents are used in CML and GIST?

Answer 5

BCR-Abl and cKIT inhibitors

- Imatinib, dasatinib, nilotinib

Question 6

What are the SEs of specific chemo in Melanoma?

Answer 6

> BRAF inhibitors combined with MEK inhibitors due to resistance
-BRAF- Vemurafenib, dabrafenib, encorafenib
-MEK- trametinib, cobimetinib, binimetinib
-Fever, dermatological (rash, hyperkeratosis, photosensitivity to UVA), skin SCC (common)/skin papilloma/keratocanthomas
PD-1 inhibitors and CTLA-4 inhibitors
-PD-1 inhibitors- nivolumab, pembrolizumab, atezolizumab, CTLA-4 inhibitors- ipilimumab.
-Induction of autoimmune disease in any organ system (e.g. pneumonitis, hepatitis)
-hypo/hyperthyroidism, colitis, hypophysitis, nervous system (Mx- steroids)

Question 7

What are the SEs of specific chemo in Breast Ca?

Answer 7

> Selective oestrogen receptor modulator: Tamoxifen
-for ER+ve
-Hot flushes, low libido, VTE, endometrial cancer (improves BMD)
Aromatase inhibitors: Anastrozole, letrozole, exemestane
-for ER+ve
-Hot flushes, low libido, arthralgia, joint pain, osteopenia/osteoporosis (no increased risk of VTE or endometrial cancer)
HER2 antibodies
-Trastuzumab, pertuzumab
-Cardiac (reduction in EF)
PARP inhibitors - Olaparib, veliparib
- Myelosuppression

Question 8

What are SEs of chemotherapy for metastatic CRC and NSCLC?

Answer 8

> EGFR monoclonal antibodies
-Cetuximab, panitumumab; gefitinib, erlotonib
-Acne/rash (severity correlates with efficacy)
VEGF antibodies
-Bevacizumab
-HTN (severity correlates with efficacy), GI perforation, impaired wound healing, tumour associated haemorrhage, arterial thromboembolic events (CVA/AMI)

Question 9

What are SEs of chemotherapy for prostate Ca?

Answer 9

> GnRH agonist/antagonist & Androgen receptor inhibitor (steroidal, non- steroidal)
-Agonist-goserelin, triptorelin, leuprorelin (AKA leuprolide), -Antagonist- degarelix
-Nont-steroidal- enzalutamide, flutamide, bicalutamide, nilutamide.
-Steroidal- cyproterone acetate
-SEs: Hot flushes, impotence/reduced libido, metabolic syndrome, osteoporosis, anaemia, reduced mood/cognition
Androgen biosynthesis inhibitor (Abiraterone)
-Abiraterone SEs: Syndrome of apparent minerocorticoid excess- hypokalaemia, HTN, fluid overload (give with steroid e.g. prednisolone)

Question 10

SEs of Cyclophosphamide

Answer 10

• Hematologic toxicity (cytopenias)
• infertility/teratogenicity
• bladder toxicity (haemorrhagic cystitis, bladder cancer; reduced with hydration and MESNA which neutralizes acrolein metabolite)
• malignancy induction (haematological and skin)

Question 11

SEs of Platins (cisplatin, oxaplatin)

Answer 11

> Cisplatin
-nephrotoxicity, ototoxicity
-peripheral neuropathy (symmetrical, distal, sensory, axonal)
Oxaplatin
-dose-dependent peripheral neuropathy (symmetrical, distal, sensory, axonal)
-acute neuropathy after each dose (cold-induced perioral paraesthesias, pseudolaryngopharyngeal dysaesthesia- discomfort swallowing cold items; sensitivity to touching cold items; paresthesias and dysesthesias of the hands, feet, and perioral region; and muscle cramps)

Question 12

SEs of Fluoropyrimidine

Answer 12

• 5-fluorouracil (IV), capecitabine (po)

- Cardiac toxicity (due to coronary vasospasm), plantar palmar erythema (hand foot syndrome)

Question 13

SEs of Taxanes (docetaxel, cabazitaxel)

Answer 13

• Sensory peripheral neuropathy

- alopecia

Question 14

SEs of Vinca alkaloids (vincristine, vinblastine)

Answer 14

-Peripheral neuropathy (axonal, sensory and motor)

Question 15

SEs of Anthracycline (daunorubicin, doxorubicin)

Answer 15

-Cardiotoxicity (reduced LVEF)

Question 16

SEs of Methotrexate

Answer 16

• alopecia, rash
• hepatitis
• pneumonitis, pulmonary fibrosis
• Nephrotoxicity (unlikely at low-dose 7.5-25mg weekly but occurs at cyclic high dose 1g or more for malignancy)
• cytopenias

Question 17

Lung cancer history - GO!

Answer 17

> D: SCLC- Limited or extensive, NSCLC (adenocarcinoma, squamous cell, large cell carcinoma)- stage, localised or metastatic
R: Smoking, occupational exposure (asbestos), chronic scarring (TB, scleroderma, ILD)
P: Cough, dyspnoea (exercise tolerance), haemoptysis, recurrent pneumonia, weight loss, anorexia, lethargy
I: CXR, CT chest, Sputum cytology, Biopsy (bronchoscopy washing cytology and biopsy, CT guided FNA, if pleural effusion- thoracocentesis or pleural biopsy, LN biopsy); Stage: CT/PET, MRIB, PFT (FEV1>1.5L for pneumonectomy)
M: SCLC: Chemo +/- RT. If response- prophylactic cranial radiotherapy. Palliative care referral
-NSCLC-Stage 1-3: Surgery- Stage 1-2 resectable. Stage 3a occasionally if no mediastinal LN. Lobectomy or pneumonectomy. If 1b (>4cm)/2/3- adjuvant cisplatin and vinorelbine; If non-resectable- chemoradiotherapy
-NSCLC-Stage 4: Palliative care improves survival, EGFR/ALK -ve chemo/immunotherapy (PD1-i second line); EGFR or ALK inhibitor if either +ve
Cx of chemotherapy, RT- secondary malignancies

Question 18

Breast cancer history - GO!

Answer 18

> R: Age, PHx, FHx, ovarian cancer, previous irradiation, oestrogen, nulliparity, early menarche, late menopause
I: Screening- second yearly mammo 50-74, annual mammo from 40 if first-degree relative <50 years, if high risk- individualised- MMG, US, MRI; Genetic- BRCA; Biopsy- ER, PR, HER2; Staging; Monitoring- TTE
M: Localised- Surgery- wide local excision+RT equivalent to mastectomy. If sentinel node +ve axillary clearance;
- Endocrine rx, chemo, herceptin (localised and metastatic)
- Radiotherapy- main indications- bone pain, SCC, cerebral metastases, ulcerating skin/primary lesions
- Skeletal protection- denosumab > bisphosphonates
- Follow up- annual mammogram; Support groups
C: Post-op lymphoedema, RT skin cx, Chemo peripheral neuropathy, myelosuppression, amenorrhoea; endo Cx- osteoporosis, vasomotor symptoms, sexual problems, vaginal atrophy, dyspareunia, early menopause, weight gain, Depression

Question 19

How are endocrine, chemotherapy, herceptin and PARP inhibitors used in Breast Ca?

Answer 19

• Basal like- triple negative, high proliferation- chemotherapy
• HER2+ - herceptin + chemotherapy (except <5mm and node negative) +/- endocrine therapy; transtuzumab + pertuzumab + taxane
• Luminal A- strongly ER/PR positive, HER2 negative, low proliferation- endocrine therapy
• Luminal B- ER or PR positive, HER2 negative, high proliferation- chemotherapy + endocrine treatment
• BRCA/triple negative - PARP inhibitors or chemotherapy

Question 20

Prostate cancer history - GO!

Answer 20

> R: Age
I: Screening- PSA remains controversial (PSA used for treatment follow up); Staging- bone scan, CT CAP, MRI prostate and pelvis
M: Localised-Radical prostatectomy, EBRT(external beam radiotherapy), brachytherapy or surveillance (if low risk/low life expect.) (prostatectomy and RT outcomes similar)
-Adjuvant- androgen deprivation therapy, RT (in combination with ADT)- if +ve margins or extraprostatic extension, no chemotherapy
M: Metastatic - ADT(surgical orchidectomy, medical orchiectomy e.g. GnRH agonist) +/-docetaxel (improves survival but also more toxicity)
-RT- bone pain, palliation of symptoms secondary to locally progressive disease, or spinal cord compression
-Bisphosphonates- zoledronic acid (or denosumab)- CRPC with bony metastases

Question 21

Colorectal cancer history - GO!

Answer 21

> R: Age, IBD (UC>CD), physical inactivity, diet, obesity, T2DM
I: Screening- FOBT q 2yrs 50-70 (5 yrly colon. if FHx)
-Surveillance: LOW risk (1-2 adenomas, <10mm, no villous features, no high grade dysplasia)- colonoscopy 5 years;
-HIGH risk (3-4 adenomas, ≥10mm, villous features, high grade dysplasia)- colonoscopy 3 years
-≥5 adenomas- colon. 1 year
-≥10 adenomas- colon. <1 year;
-Colonoscopy + biopsy
-CEA, CT C/A/P, if rectal cancer- MRI to assess local extent
M: CRC- surgery then adjuvant (5-FU + oxaliplatin); Rectal cancer- neoadjuvant chemoradiotherapy prior to operation (for T3/4 or N+ tumours) followed by adjuvant chemo; Metastatic- surgery if resectable metastases, chemo +/- immunotherapy
F/up: Colonoscopy- at 12 months then 3-5 yearly if normal
- CEA- 3 monthly for 2 years then 6 monthly
- CT- yearly for 3 years

Question 22

Skin/melanoma history - GO!

Answer 22

• P: Asymmetric, border irregularity, colour variegation, diameter >6mm, enlarging/evolution
• I: Screening not routine- screen only high risk groups- skin check (no RCTs conducted to demonstrate efficacy/ mortality reduction); Excisional biopsy; Stage 1- no other tests, stage 2-4- staging- sentinel node biopsy, MRI Brain, CT CAP, PET
• M: Stage 3- immunotherapy (not on PBS); Stage 4- surgery if resectable metastases, chemotherapy not used, radiotherapy if multiple brain metastases, immunotherapy- if BRAF mutation- BRAF inhibitor + MEK inhibitor, cKIT mutation (acral and mucosal subtypes)- imatinib, otherwise PD-1 and CTLA-4 inhibitors

Question 23

What is treatment for SCLC?

Answer 23

Local: combined chemo (etoposide + cisplatin) + RTx
Advanced: combined chemo
Prophylactic cranial irradiation

Question 24

What are paraneoplastic manifestations of SCLC?

Answer 24

• eaton-lambert
• SIADH
• ectopic ACTH
• carcinoid

Question 25

Tumour markers used in screening?
Tumour markers used in diagnosis?
Tumour markers used in staging and f/up?

Answer 25

> screening
-AFP (HCC in cirrhotics and HBV)
-PSA
-CA-125(only in high risk carriers. Combo with TVUS). No role in avg risk.
diagnosis
-AFP (Germ cell Tumours/ HCC)
Staging and f/up
-CEA: prognostic significance, 3-6/12ly up to 5yr
-AFP
-PSA detects biochemical recurrence before clinical; 6-12 monthly for 5y, then annually
-CA-125 - response to Rx
-CA 19.9; CA 15.3 - monitor progression; and response in metastatic disease

Question 26

Carcinoid syndrome history - GO!

Answer 26

> D: neuroendocrine tumours of GI tract and lungs
-serotonin, histamine, tachykinins, kallikrein, prostaglandins
- GI are metastatic, as need to bypass the liver to causes symptoms (90% ileum/appendix to liver); whereas bronchial tumours still be localised
P: Cutaneous flushing - episodic flushing classic
-Venous telangiectasia
-Diarrhoea - Secretory diarrhoea occurs in 80%
-Bronchospasm - beta agonists like adrenaline can trigger this and hypotension (often fluctuating hypotension)
-R-side Cardiac valvular lesions, carcinoid deposits, fibrosis
-Minor manifestations - pellagra, muscle wasting
I: elevated serum serotonin or urinary 5-HIAA in crisis; 24hr urinary 5-HIAA (hydroxyindoleacetic acid)
-localise tumour with CT abdo and somatostatin receptor scintigraphy (SRS)‘OctreoScan’.
M: Somatostatin analogs (e.g. Octreotide) for symptomatic control. Also reduces risk of carcinoid crisis.
- Liver resection/ embolisation if liver predominant
-Anti-diarrhoeal agents for diarrhoea
-Everolimus - some emerging evidence