Treatment of cancer & Oncology Emergencies Flashcards
What systemic therapy can be offered for cancer
Chemotherapy
Biologics
Hormonal therapy
Immunotherapy
What are aims of Rx
Adjuvant
Neoadjuvant
Palliative
Curative or radical
What is adjuvant
After definite and curative rx to eradicate micromets
What is neoadjuvant
Adjuvant Rx given before to improve chance of cure
What are SE of chemotherapy
Relate to rapidly dividing tissue as that is what is attacked Alopecia Mouth ulcer Diarrhoea Neutropenia Thrombocytopenia
What are 7 major classes of systemic chemotherapy
- Alkylating agent - disrupt DNA integrity
- Anti-metabolites - disrupt DNA synthesis
- Mitotic inhibitor (vinca alklaloid) disrupt microtubule function
- Toposomerase inhibitor - regulate DNA unwinding
- Platinums cause cross linking of DNA strands
- Taxanes disrupt microtubule function
- Anthracyclines intercalate between base pairs in RNA/DNA thereby preventing synthesis.
What are anti-metabolites
- Purine (fludarabine)
- Pyrimidine (5-fluorouracil,
- gemcitabine)
- Folate (methotrexate, pemetrexed)
what are aklyating agent
Cyclophosphamide
Ifosfamide
Give examples of mitotic inhibitor or vinca alklaloids
Name one common side effect
- Vincristine
- Vinblastine
- SE: neuropathy
What is topoisomerase inhibitor / Ax
Etoposide
Irontecan
What is a common SE of alkylating agents
Haemorrhagic cystitis
What are common SEs of anthracyclines [3]
What are 2 examples: doxorubicin, epirubicin
Side effects
* Myelosuppression
* Cardiotoxicity
* Leukaemia (doxorubicin)
SE of bleomycin
Lung fibrosis
SE of Anti-metabolites
SE of methotrexate
- Hepatotoxicity
- Ulcerative stomatitis
- Pneumonitis, pulmonary fibrosis (methotrexate).
SE of 5-FU
Myelosuppression
Mucositis
Dermatitis
What does vinblastine / docetaxel do and what are SE
Inhibit formation of microtubule Peripheral neuropathy Paralytic ileus Myelosuppression Neutropenia = docetaxel
SE of cisplatin
Ototoxicty
Peripheral neuropathy
HypoMg
SE of hydroxyurea
Myelosuppresson
What do biologic agents do and what are there categories
Inhibit orogenic stimulus that is driving cancer growth
Monoclonal Ab - imab
Tyrosine kinase inhibitors - inib
What is ritixumab useful for
Anti-CD20 so useful in B cell lymphoma which express
What has revolutionised CML Philadelphia chromosome +ve
Imatinib
What causes ligand inactivation
Bevacilumab
Stops VEGF which is over expressed in many cancer
What cause receptor inactivation
Tratuzumab against HER-2
What hormone therapy in breast
Anti-oestrogen - tamoxigen
Aromatose inhibitor
GnRH agonist (goserelin)
What hormone therapy in prostate cancer
Androgen suppression - goserelin or orchidectomy
Anti-androgen
What hormone therapy in endometrial
Progesterone
What is systemic immunotherapy
Stimulates whole immune system
Interferon
Interluekin
What are toxicity interferon
Flu like Nausea Lethargy Anorexia LFT
What are toxicity IL
Hypotension
Renal failure
Cardiac - may need ITU
How do many cancers evade detection
Suppress T cell function through PD-1 on T cell or PDL-1 on tumour
What Ab target this
PD-1 Ab - nivolumab / pemprolizumab
PDL-1 Ab - atezolizumab
What are SE related to overactive T cells which are key in killing cancer
Dry / itchy skin = most common N+V Decreased appettite Diarrhoea Fatigue SOB Dry cough
What is radiation dose
Energy deposited per unit mass = absorbed dose (Gray)
1 gray = 1 joule of energy in 1kg
What is radiation tolerance
Amount of radiation tissue can receive and still remain functional
What is tolerance dose
Dose that there is a high probability of serious Rx compliction
What is external beam
Most common
Linear accelerator delivers X-ray
What is sealed source
Radioactive need or wile implanted into or next to cancer for extremely high dose
What does a PET scan do
Uses FDG radio tracer allowing 3D image of metabolic activity / uptake of glucose
Combines images with CT
Radiotherapy early side effects [7]
Tiredness Skin reactions eg erythema, ulceration Mucositis Nausea and vomiting, diarrhea Dysphagia Cystitis Bone marrow suppression (large areas)
Targeting radiotherapy
Describe the difference between conformal radiotherapy and intensity modulated radiotherapy.
- Conformal radiotherapy- the target volume and normal tissues are delineated on a CT scan. The position of the radiotherapy beams is then chosen to optimise the radiation dose to the tumour and limit radiation to normal tissue thus reducing toxicity. Lead shielding may be used to help reduce the dose to normal tissues.
- Intensity modulated radiotherapy (IMRT) uses advanced computer programmes to modulate intensity of the radiation beam at different sites, helps to shape the radiation beam more accurately, particularly around concave structures.
What is stereotactic radiotherapy and when is it used?
- Stereotactic radiotherapy involves combining highly conformal radiotherapy, usually with multiple radiation beams, with very precise treatment delivery.
- This type of radiotherapy gives a high dose of radiation in a small number of treatments (≤5).
- In tumours that are small and well-defined, stereotactic radiotherapy may result in long-term efficacy (e.g. small brain metastases, liver metastases).
What is most common cause of spinal cord compression [6]
Breast Lung Prostate Renal Thyroid Myeloma
Where in spine is affected [2]
** vertebral collapse or extradural vertebral body mets.
** MSCC occurs in up to 5% of patients with cancer, and is the presenting feature in up to 20% of patients with an underlying malignancy.
* The risk of MSCC is higher in cancers with a known propensity for bone metastases
usually thoracic spine (can also get due to tumour extension from vertebral body)
Presentation of malignant spinal cord compression [4]
- thoracic back pain in a radicular distribution worsening over preceding weeks or months
- worse on coughing, sneezing and weight bearing, or lying flat, localised spinal tenderness
- bladder/bowel dysfunction
- new weakness climbing stairs
If above L1
UMN signs + sensory
Immediate management [5]
- lie flat until spinal stability determined
- catheter if retention
- prophylactic DALTEPARIN
- bisphosphonates in breast cancer or myeloma
- DEXAMETHASONE + PPI
- Urgent MRI 24 hours and spinal surgical referral
Definitive management of Malignant SCC
Decompression and stabilisation
= gold standard
When is radiotherapy and what type is used for MSCC?
External beam radiotherapy represents the treatment of choice when surgical decompression is not possible and should be commenced as soon as possible.
How do you investigate spinal cord compression [4]
MRI whole spine = gold standard
Isotope bone
FBC, U+E, LFT, Ca, PSA, LDH
Myeloma screen
What is most common cause of SVC obstruction [3]
What is the test used in examination to identify?
SCLC
NSCLC
Lymphoma
Pemberton’s test: lifting arms above head for >1 min causes facial plethora or cyanosis, elevated JVP and inspiratory stridor
Superior vena cava obstruction
Aetiology of SVCO
Superior vena cava obstruction (SVCO) occurs when there is obstruction of blood flow though the superior vena cava (SVC) due to
* internal thrombosis, tumoural invasion or external compression.
* The consequent increase in venous pressure in the upper body results in tissue oedema with airway obstruction and cerebral swelling.
* If gradual compression of the SVC occurs then development of collateral vessels draining into the inferior vena cava system may compensate for the obstruction
* Central venous access devices are also a risk factor; thrombotic occlusions are more frequently related to PICC lines due to inadequate catheter tip placement than portacath/Mediport devices.
SVC obstruction
Symptoms [6]
Signs [4]
Symptoms:
- SOB
- Facial swelling/head fullness
- Arm swelling
- Dysphagia
- Orthopnoea
- Headache
Signs:
- Distention of neck and chest wall veins
- Fixed elevated JVP
- Plethora/cyanosis
- Peripheral cyanosis
How do you investigate SVC obstruction [4]
CXR
Contrast enhanced CT is imaging modality of choice
Doppler ultrasound - thrombus in axillary/subclavian veins
FBC, clotting profile (extensive thrombosis assoc with platelet sequestration)
How do you manage SVC obstruction [3]
depends on the cause
- caused by lines then anticoagulation
- shrink mass and reduce compression
- unknown primary then biopsy
- symptomatic measures: dexamethasone, diuretics, sit up to reduce orthostatic pressure.
What is most common life threatening disorder associated with malignancy
Hyperclacaemia
Bad prognostic indicator
Two mechanisms of hypercalcaemia in cancer
Bone mets increasing osteolytic activity - Breast - MM Or production of PTH by tumour - SCC - T cell lymhpoma
What are the features of hypercalcaemia [6]
‘bones, stones, abdominal groans and psychic moans’
- polydipsia, polyuria
- peptic ulceration/constipation/pancreatitis
- bone pain/fracture
- renal stones
- depression
- hypertension
What can hypercalcaemia be mistaken for
Terminal feature of cancer
What does chemo result in
Neutropenia
Often day 7-14 days but can be 6 weeks
What causes increase risk
<1 x10 ^9 but extreme = -.5
What is neutropenic sepsis
Evidence of sepsis - hypo / tachy
Neutrophil <1
With or without fever
How do you investigate
FBC, U+E, LFT, CRP Bone bloods Coag if DIC suspected Blood culture MSSU Stool culture if diarrhoea Throat swab Sputum culture Skin swab CXR LP / CT ECG
How do you manage [5]
As emergency IV access Fluid resus O2 Broad spec Ax
Neutropenic sepsis
Management of persistent pyrexia
Management of prolonged neutropenia
- If persistent pyrexia occurs despite appropriate treatment, second-level investigations may be considered, for example, HRCT scan of the chest ± broncho-alveolar lavage.
- (e.g. haematopoietic transplant patients) who are at risk of fungal infections, and who do not respond to broad spectrum antibiotics, but who remain febrile after 3–5 days should receive empiric anti-fungal therapy
When do you change to oral [2]
3 days IV Ax and improving
Oral ciprofloaxicin
What can you consider
G-CSF
reduce duration of neutropenia and length of hospital stay.
Tumor lysis syndrome Ax
Name 4 cancers that are high risk of TLS, 4 risk factors.
- Tumour lysis syndrome (TLS) occurs when a large number of rapidly proliferating cells die leading to release of high volumes of intracellular components such as nucleic acids and other intracellular metabolites.
- TLS usually occurs during the first cycle of chemotherapy, but may arise spontaneously.
- The malignancies that are most commonly affected are high-grade haematological malignancies
- Other risk factors include high LDH, bulky disease, high white cell count, high uric acid and pre-existing renal impairment.
- Burkitt lymphoma
- Leukemia
- Myeloma
- Germ cell tumours
TLS mx [3]
Prevention [2]
- IV RASBURICASE
- CALCIUM GLUCONATE (if symptomatic hypocalcaemia)
- renal dialysis if intractable
Prevention
IV ALLOPURINIOL or IV RASBURICASE (recombinant urate oxidase which metabolises uric acid to allantoin)
SVCO
Emergency management of SVCO if patients are at high risk of sudden respiratory failure or symptomatic cerebral oedema
endovascular stent placement will provide more immediate relief of pressure than radiotherapy or chemotherapy.
What is the Cairo-Bishop criteria
Diagnosis of TLS
The Cairo–Bishop criteria for diagnosis of biochemical TLS requires the presence of ≥2 of the following abnormalities in a patient with cancer, or undergoing treatment for cancer, within 3 days prior to and up to 7 days after initiation of treatment:
Uric acid, potassium, phosphate, calcium if 25% increase from baseline.
Testicular cancer & biomarkers
Seminomas
Non-seminoma
seminomas: seminomas: hCG may be elevated in around 20%
non-seminomas: AFP and/or beta-hCG are elevated in 80-85%
Psoriasis treatment
What kind of skin cancer is caused by psoralen + ultraviolet A light therapy?
PUVA therapy, which involves the use of psoralen (a photosensitizing medication) and ultraviolet A light, has been associated with an increased risk of squamous cell carcinoma. This is due to the mutagenic effect of UVA radiation on keratinocytes when used in conjunction with psoralen. The risk is particularly high in patients who have received a high cumulative dose of PUVA or those who have fair skin.
What is the most common type of Hodgkins lymphoma?
Nodular sclerosing
Management of gastric MALT lymphoma
Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is a type of non-Hodgkin lymphoma that arises from the mucosal lymphoid tissue of the stomach. It has been found to be strongly associated with chronic H. pylori infection, which induces a local inflammatory response and subsequent development of MALT in the gastric mucosa. According to UK guidelines, initial treatment for localised gastric MALT lymphoma should be aimed at eradicating H. pylori, irrespective of the patient’s H. pylori status. This can lead to regression of the tumour in a significant proportion of patients.
Acanthosis Nigricans
Associated Malignancy: Gastric Cancer
Acquired Ichthyosis
Associated Malignancy: Lymphoma
Acquired Hypertrichosis Lanuginosa
Associated Malignancies: Gastrointestinal and Lung Cancer
Acquired hypertrichosis lanuginosa is also referred to as ‘hypertrichosis lanuginosa acquisita’, ‘paraneoplastic hypertrichosis lanuginosa’ and ‘malignant down’.
Dermatomyositis
Associated Malignancies: Ovarian and Lung Cancer
Erythema Gyratum Repens
Associated Malignancy: Lung Cancer
Erythema gyratum repens is a rare paraneoplastic type of annular erythema with a distinctive figurate ‘wood-grain’ appearance. It has a strong association with malignancy.
Erythroderma
Associated Malignancy: Lymphoma
Migratory Thrombophlebitis
Associated Malignancy: Pancreatic Cancer
Necrolytic Migratory Erythema
Necrolytic migratory erythema may affect any site but it most often affects the genital and anal region, the buttocks, groin and lower legs. The rash fluctuates in severity. Initially there is a ring-shaped red area that blisters, erodes and crusts over. It can be quite itchy and painful. As it heals, it may leave behind a brown mark.
Associated Malignancy: Glucagonoma
Pyoderma Gangrenosum (Bullous and Non-bullous Forms)
Associated Malignancy: Myeloproliferative Disorders
Sweet’s Syndrome
Acute febrile neutrophilic dermatosis is an uncommon skin condition characterised by fever and inflamed or blistered skin and mucosal lesions. Neutrophilic dermatoses are autoinflammatory conditions often associated with systemic disease.
Associated Malignancy: Haematological Malignancy (e.g., Myelodysplasia - tender, purple plaques)
Tylosis
Focal keratodermas are palmoplantar keratodermas (PPK) that involve only some areas of the palms or soles, usually over pressure points. Some types are associated with abnormalities in organs other than the skin.
Associated Malignancy: Oesophageal Cancer
Multiple Endocrine Neoplasia (MEN)
MEN type 1
MEN type IIa
MEN type IIb
Describe the genetic mutation of each
Describe MEN type I
3 P’s
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid
Most common presentation = hypercalcaemia
Describe MEN type II and MEN type IIb
cytogenetics of haematological malignancies
?CML
APML
AML - poor prognosis
NHL
BCR-ABL fusion gene
APML Ch 15, 17
Ch5 carries poor prognosis in AML
Ch 9 and 14 translocation - NHL
Paraneoplastic features of lung cancer
squamous cell?
small cell?
Paraneoplastic features of lung cancer
squamous cell: PTHrp, clubbing, HPOA
small cell: ADH, ACTH, Lambert-Eaton syndrome
