Oncology AS Flashcards
Familial Breast and Ovarian Cancer
~10% of breast Ca is familial
~5% is caused by BRCA1 or BRCA2 mutations.
- Both TSGs
- BRCA1: Breast Ca ~80%, Ovarian Ca ~40%.
- BRCA2: Breast Ca ~80%, male breast Ca + prostate cancer
May opt for prophylactic mastectomy and oophrectomy
Familial Prostate Ca
- ~5% of those with prostate Ca have +ve fam HX
- Multifactorial inheritance
- BRCA1/2 –> moderately increased risk.
Familial CRC
- ~20% of those with prostate Ca have +ve Fam history.
- Relative risk of CRC for individual with FH related to:
Closeness of relative
Age of relative when Dx.
Types of familial CRC?
- Familial Adenomatous Polyposis
- HNPCC
- Peutz-Jehgers
What is FAP?
Familial Adenomatous POlyposis
- Mutation in APC gene on Chr 5
- TSG
- Promotes B-catenin degradation
Cells then acquire another mutation to become Ca (p53/kRAS).
- AD transmission
- ~100% risk of CRC by 50yrs.
What is HNPCC?
Familial clustering of cancers - Lynch 1: CRC - Lynch 2: CRC + other Ca Ovarian Endometrial Pancreas Small Bowel Renal pelvis
Mutations iN DNA mismatch repair gene
AD transmission
Often Right-sided CRC
Present @ young age: <50yr.
What is Peutz-Jegher’s
- AD transmission
- Multiple GI hamartomatous polyps
- Mucocutaneous hyperpigmentation
(lips, palms). - 10/20% lifetime risk of CRC
- Also increased risk of other Ca
Pancreas
Lung
Breast
Ovaries and Uterus
Testes.
Oncological emergencies - Febrile Neutropenia?
PMN < 1x10^8
- Isolation + barrier nursing
- Meticulous antisepsis
- Broad-spectrum Abx, anti-fungal, anti-virals
- Prophylaxis: co-trimoxazole.
Oncological emergencies - Spinal Cord compression?
Presentation
- Back pain, radicular pain
- Motor reflexes and sensory level
- Bladder and bowel dysfunction
Causes of Spinal cord compression?
- Usually extradural metastasis
- Crush fracture
Investigations of spinal cord compression
Urgent MRI spine
Spinal cord compression management?
- PO Dexamethasone 8mg BD
- Discuss with neurosurgeon and oncologist
- Consider radiotherapy or surgery
SVCO with airway compromise?
SVCO not an emergency unless there’s tracheal compression with airway compromise.
Causes of SVC compression?
- Usually Lung Ca
- Thymus malignancy
- LNs
- SVC thrombosis: central lines, nephrotic syndrome
- Fibrotic bands: Lung fibrosis after chemo
Presentation of SVC compression?
Headache Dyspnoea and orthopneoa Plethora + thread veins in SVC distribution Swollen face and arms Engorged neck veins
What is Pemberton’s sign?
- Lifting arms above head for >1min –> facial plethora, increased JVP and inspiratory stridor
- Due to narrowing of the thoracic inlet.
Investigations of SVCO?
sputum cytology
CXR
CT
Venography
Management for SVCO?
- Dexamethasone (dex for malignancy, mannitol for everything else)
- Consider Balloon venoplasty + SVC stenting
- Radical or palliative chemo/radio.
Hypercalcaemia in Oncology?
40% of those with myeloma
10-20% of those with Ca
Due to lytic bone mets
Production of PTHrP
Symptoms of Hypercalcaemia
Confusion Renal stones Polyuria and polydipsia Abdo pain, constipation Depression Lethargy Anorexia
Investigations of Hypercalcaemia?
- Increase Ca Often >3mm
- Decreased PTH (key to exclude increased HPT)
- CXR
- Isotope bone scan.
Management of Hypercalcaemia?
Aggressive hydration
- 0.9% NS
- Monitor volume status
- Furosemide when full to make room for more fluid.
If primary HPT excluded, give maintenance therapy - bisphosphonate: Zoledronate is good.
Other oncological emergencies?
Raised ICP
Tumour Lysis Syndrome
Management of cancer - Chemotherapy?
Cancer must be managed in an MDT
- Neoadjuvant (Shrink tumour to decreased need for major surgery. Control early micromets.
- Primary therapy (sole Management in haematological cancers)
- Adjuvant
decreased change of relapse e.g breast and GI cancer - Palliative
Provide relief from symptoms
Cytotoxic Classes?
Alkylating agents Antimetabolitis Vinca alkaloids Cytotoxic ABx Taxanes Immune modulators MAbs
What are the alkylating agents
Cyclophosphamide, chorambucil, busulfan
What are the antimetabolities?
Methotrexate, 5-FU
What are the vinca alkaloids
Vincristine and Vinblastine
What are the cytotoxic antibiotics
Doxorubicin, bleomycin, actinomycin D
What are the taxans?
Paclitaxel
What are the immune modulators?
Thalidomide
Lenalidomide
What does Trastuzumab treat?
anti-Her2 breast Ca
What does Bevacizumab treat
Anti-VEGF: RCC, CRC, Lung
What does Cetuximab treat?
Anti-EGFR: RCR
What does Rituximab treat?
Anti-CD20 : NHL
What are the TK inhibitors?
Erlotinib: Lung cancer
Imatinib: CML
What are the endocrine modulators?
Tamoxifen
Anastrazole
What are the common side effects of Chemo?
n/v
Alopecia
Neutropenia
Extravasation of chemo agent
- Pain, burning, bruising at chemo infusion site
- Stop infusion, give steroids, apply cold pack
- Liaise early with plastics.
What specific problems does cyclophosphamide cause?
Hemorrhagic cystitis, myelosuppression, transitional cell carcinoma
Hair loss
BM suppression
What specific problems does Doxorubicin cause?
Cardiomyopathy
What specific problems does bleomycin cause?
Pulmonary Fibrosis
What specific problems does Vincristine cause?
Peripheral neuropathy (reversible)
Paralytic ileus
Vinblastine: Myelosuppression
What specific problems does Carboplatin cause?
Peripheral neuropathy
N/v
nephrotoxic
What specific problems does paclitaxel cause?
Hypersensitivty
What is Radial Radiotherapy treatment
- Curative intent
- 40-70Gy
- 15-30 daily fractions
What is palliation radiotherapy ?
Symptoms relief
- Bone pain, haemoptysis, cough, dyspnoea, bleeding
8-30 Gy
1-10 fractions.
What are the early reactions to radiotherapy?
Tiredness Skin reaction: erythema --> ulceration Mucositis (painful ulceration and damage to mucous membranes) N/V Diarrhoea Cystitis BM suppression
Late reactions for radiotherapy?
Brachial plexopathy
- follows axillary radiotherapy
- Numb, weak, painful arm
Lymphoedema
Pneumonitis
- Dry cough ± dyspnoea
- manage: prednisolone
Xerostomia Benign strictures Fistulae Decreased fertility Panhypopituitarism
Surgery for cancer therapy
Diagnostics: tissue biopsy
Excision: GI, soft-tissue sarcoma, gynae
Palliation: Bypass procedure, stenting.
What malignant cancers is AFP used for?
Hepatocellular carcinoma
Teratoma
What non- malignant conditions is AFP a marker for?
Hepatitis
Cirrhosis
Pregnancy
What malignant cancers is CA125 used for?
Ovary
Uterus
Breast
Should be part of a work up for non-specific abdo pain. Ovarian can fill much of the abdominal cavity. May be hard on a CT scan to convincingly identify primary.
Screen for FBC, U+E, LFTs, Calcium, Urinalysis, LDH, AFP, hCG.
What non-malignant conditions is CA125 used for?
Cirrhosis
Pregnancy
What malignant cancers is Ca15-3 used for?
Breast
What non-malignant conditions is Ca15-3 used for?
Benign breast diseaase
What malignant cancers is Ca19-9 used for?
Pancreas
Cholangiocarcinoma
CRC
What non-malignant cancers is Ca19-9 used for?
Cholestatis
Pancreatitis
What malignant cancers is Ca 27-29 used for?
Breast
What malignant cancers is Neuron-Specific enolase used for?
SCLC
What malignant cancers is CEA used for?
CRC - colorectal cancer
What non-malignant conditions is CEA used for?
Pancreatitis
Cirrhosis
What malignant cancers is B-HCG used for?
Germ cell tumours
AFP and HCG normally raised in non-seminoma but normal in seminoma
In non-seminomas (Teratoma) AFP is raised in 70% and hCG raised 40%. Man takes gfs pregnancy test and finds out he has a teratoma.
What malignant cancers is PSA used for?
Prostate (non-malignant = BPH)
What malignant cancers is mono Ig used for?
Multiple Myeloma
What malignant cancers is S-100 used for?
Melanoma (benign in Sarcoma)
What malignant cancers is PLAP used for?
Seminoma
What malignant cancers is acid phosphatases used for?
Prostate
What malignant cancers is thyroglobulin used for?
Thyroid cancer
Bombesin
Small cell lung carcinoma
Gastric cancer
Neuroblastoma
Spinal cord compression
Oncological emergency
- 5% of cancer patients. Extradural compression accounts for majority of cases.
- Back pain, earliest and most common symptom. Worse on lying down or coughing.
- Lower limb weakness
- Sensory changes: sensory loss and numbness
- Neuro signs depend on level of lesion.
- Lesion above L1 usually result in UMN signs in the legs + sensory level.
- Lesions below L1 usually cause LMN signs in legs + perianal numbness
- Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion.
Management
- High-dose oral dexamethasone
- Urgent oncological assessment for consideration of radiotherapy or surgery.
Irinotecan (Topoisomerase I)
Myelosuppression
Cisplatin SE
Ototoxicity,
peripheral neuropathy,
Hypomagnesaemia
Hydroxyurea SE
Myelosuppression
Toxicity Bear?
A = Asparagine (neurotoxicity)
Cisplatin = ototoxicity/ nephrotoxicity - Tx = amifostine
Vincristine = Christ my nerves (peripheral neuropathy w/ vincristine), blast my bones (myelosuppression with vinblastine)
Bleomycin = Pulmonary fibrosis
Doxorubicin = Cardiomyopathy; tx = dexrozoxane
Cyclophosphomide = Nephrotoxicity, hypomagnesaemia, bladder toxic. Tx = democycline
Methotrexate: nephrotoxicity, (tx: leucovorin), myelosuppression (tx: filgrastim), oral mucositis, liver fibrosis
Nivolumab MOA and use?
Immune checkpoint inhibitor = PD-1. Treatments for melanoma, Hodgkin’s lymphoma, NSCLC, uro cancers
Ipilimumab MOA and use?
CTLA-4 (cytotoxic T lymphocyte-associated protein 4 for melanoma.
Given via injection/IV infusion.
Atezolizumab, Avelumab, Durvalumab use?
PD-L1 - treat lung cancer and urothelial cancer.
Side effects of checkpoint inhibitors?
Dry, itchy skin and rashes (most commonly) Nausea and vomiting Decreased appetite Diarrhoea Tiredness and fatigue Shortness of breath and a dry cough.
Immune related problems.
Woman with bone mets causes?
Most likely to come from breast cancer.
Likelihood =
Prostate
Breast
Lung
Most common site
- Spine
- Pelvis
- ribs
- Skull
- Long bones
Most common cancers?
- Breast
- Lung
- Colorectal
- Prostate
- Bladder
- Non-Hodgkin’s lymphoma
- Melanoma
- Stomach
- Oesophagus
- Pancreas
Most common cause of death from cancer?
- Lung
- Colorectal
- Breast
- Prostate
- Pancreas
- Oesophagus
- Stomach
- Bladder
- Non-Hodgkin’s lymphoma
- Ovarian
For patients at low-ris of symptoms of nausea and vomiting?
Use metaclopramide
For high-risk patients - 5HT3 receptor antagonist such as ondansetron - especially if combined with dexamethasone.
For intracranial tumours -> dexamethasone
Features of spinal mets?
- unrelenting lumbar back pain
- any thoracic/ cervical back pain
- worse with sneezing, coughing or straining
- nocturnal
- a/w tenderness
If any neuro sx -> consider cord compression
Commonest lung cancer in non-smokers?
Adenocarcinoma
- typically peripheral
- commonest cancer in non smokers
Calcitonin a marker for?
Medullary thyroid cancer (MaiCa)
Thyroglobulin a marker for?
Follicular/ papillary cancer (fthapad)
Features of Gardner’s syndrome?
- Autosomal dominant familial colorectal polyposis
- Multiple colonic polyps
- Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
- Desmoid tumours are seen in 15%
- Mutation of APC gene located on chromosome 5
- Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
- Now considered a variant of familial adenomatous polyposis coli
Features of Li Fraumeni syndrome?
- Autosomal dominant
- Consists of germline mutations to p53 tumour suppressor gene
- High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:
- Individual develops sarcoma under 45 years
- First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age
Features of lynch syndrome?
- Autosomal dominant
- Develop colonic cancer and endometrial cancer at young age
- 80% of affected individuals will get colonic and/ or endometrial cancer
- High risk individuals may be identified using the Amsterdam criteria
Amsterdam criteria
> Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two.
> Two successive affected generations.
> One or more colon cancers diagnosed under age 50 years.
> Familial adenomatous polyposis (FAP) has been excluded.
Investigating an unknown primary?
NICE recommends the following investigations for all patients:
- FBC, U&E, LFT, calcium, urinalysis, LDH
- Chest X-ray
- CT of chest, abdomen and pelvis
- AFP and hCG
NICE recommends the following investigations for specific patients:
- Myeloma screen (if lytic bone lesions)
- Endoscopy (directed towards symptoms)
- PSA (men)
- CA 125 (women with peritoneal malignancy or ascites)
- Testicular US (in men with germ cell tumours)
- Mammography (in women with clinical or pathological features compatible with breast cancer)