Palliative / Oncology / Haematology Flashcards
Classical Side Effects of Chemotherapeutics?
Anthracyclines (doxorubicin, daunorubicin) and anti-HER-2 monoclonal antibodies (e.g. Herceptin) cause cardiomyopathy.
Platinum agents (cisplatin, carboplatin) cause peripheral neuropathy and sensorineural hearing loss.
Cyclophosphamides lead to haemmorhagic cystitis and transitional cell carcinoma of the bladder.
Tamoxifen increases the risk of endometrial cancer (both an oestrogen agonist and antagonist (i.e SERM) - antagonist in breast tissue/ agonist in endometrial and bone tissue - prevents osteoporosis).
Bleomycin can cause lung fibrosis and Gemcitabine - pneumonitis
Cisplatin has a risk of ototoxicity and nephrotoxicity
Cytarabine can cause ataxia
5-FU Palmar erythema (hand and foot) and coronary vasospasm
_____ is associated with peripheral neuropathy and is a common therapeutic agent in non-Hodgkin’s lymphoma.
Vincristine
Vincristine is a chemotherapy drug that belongs to a group of drugs called vinca alkaloids. Vincristine works by stopping the cancer cells from separating into 2 new cells. So, it stops the growth of the cance
Lung cancers can be divided into small-cell and non-small cell tumours. The most common histological type of tumour is ____ , followed by _____ cancer.
adenocarcinoma
squamous cell
Hypertrophic pulmonary osteoarthropathy (HPOA) is a syndrome characterized by the triad of ____, _____ and _____ of the large joints, especially involving the lower limbs.
periostitis
digital clubbing
painful arthropathy
HPOA (Hypertrophic pulmonary osteoarthropathy) this occurs in 3% of cases. There will be joint stiffness, and severe pain in the wrists and ankles, sometimes also gynaecomastia.
On x-ray there will be proliferative periostitis at the ends of the long bones, which have an ‘onion skin’ appearance. This is also associated with finger clubbing where cancer is the cause. It is thought to be caused by a blood borne factor released by the tumour – when patients have the primary tumour removed, the pain goes away!
Paraneoplastic syndromes of lung cancer: Cushing’s syndrome, SIADH, and Lambert-Eaton syndrome suggest _____, whilst hyperparathyroidism suggests ____.
small-cell lung cancer
squamous cell cancer (Often causes hypercalcaemia – by bone destruction or production of PTH analogues (PTHrp).
Important features of small cell lung cancer.
Arise from ____ cells aka _____ cells. These are APUD cells, and as a result, these tumours will secrete many poly-peptides mainly ACTH.
Endocrine AKA Kulchitsky or Argentaffin (Stain) cells (Arise from the bronchus)
The _endocrine cells_ of the gastrointestinal tract are APUD cells. This acronym stands for amine precursor uptake and decarboxylation, after the classical function of the cells, which may relate to their role in hormone synthesis.
They can also cause various presentations such as Addison’s and Cushing’s disease.
Small cell carcinoma spreads very early and is almost always inoperable at presentation.
These tumours do respond to chemotherapy, but the prognosis is generally poor.
**Carcinoid syndrome is the collection of symptoms some people with a neuroendocrine tumour may have**
Lung cancer commonly metastasises to the___ , ___, ___ and ____.
The most likely mechanism by which brain metastases spread is via the bloodstream.
brain
breast
adrenals
bone
_____ is the correct antibiotic regimen for neutropenic sepsis.
IV Tazocin (piperacillin and tazobactam)
(often presents post chemotherapy in a neutropenic or immunosuppressed patient)
Remember if patient is admitted for IV antibiotics and sepsis always stop chemotherapy tablet that they are on!
Clinical features of Immunotherapy toxicity?
Think inflammation
- Dermatological manifestations such as a pruritic maculopapular rash
- Immune colitis resulting in diarrhoea (ex. nivolumab)
- Endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism.
- Hepatitis
20-60% of people get these reactions
It is important to be able to recognise the clinical features of immunotherapy toxicity in cancer patients, as these agents now form the first line medical management for many cancers, notably metastatic melanoma and colorectal cancer.
Notably, immunotherapy toxicity is often delayed, and can occur even months after the last cycle of immunotherapy has been administered.
High dose steroids form the mainstay of management for these autoimmune events, although discussion with the oncology team would be necessary as steroids hamper treatment efficacy.
Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of small cell lung cancer shows cells with _____.
dense neurosecretory granules
_____ is the preferred contraceptive option in women and girls with PCOS
COCP
*It helps control period regularity, as well as other manifestations of the condition like acne*
What is the initial most effective initial dosing regimen of opioid analgesia in a cancer patient with persistent/worsening/severe pain?
A total daily oral Morphine dose of 30mg.
NICE recommends that a dose of 20-30 mg oral Morphine is safe and effective for opiate naïve patients initially commenced on opioid analgesia.
Though dependent on patient choice, immediate release oral morphine solution given four-hourly (i.e as 5 mg immecdiate release formulation that over 24 hrs adds up to 20-30mg - also known as Oramorph) is the recommended formulation used to initially determine a patient’s pain control requirements.
The total daily oral Morphine dose can later be converted to twice daily modified release Morphine sulphate tablets, also known as MST Continus tablets.
Most common microorganism cause of neutropenic sepsis evolving from an indwelling peripheral line?
Staphylococcus Epidermitis
This is a coagulase-negative staph, and is a common cause of line infections (particularly in neutropenic patients, from which they can develop neutropenic sepsis)
______ cancer commonly presents in elderly patients, particular women, with signs of airway compromise (stridor) and dysphagia. It is a rare but aggressive tumour
Anaplastic thyroid carcinoma
Morphine prescribed for breakthrough pain is stipulated as ____ of the total oral Morphine dose, and prescribed as instant release oral Morphine such as “Oramorph” solution.
1/6
For example the dose required for breakthrough pain for this patient is (30x2)/6 = 10mg.
*Oral Codeine is 1/10 the strength of oral Morphine*
Side Effects of Radiotherapy:
Early side effects ______
Late side effects ______
The side effects of radiotherapy are cumulative and thus occur mostly towards the end of the treatment course. Normal treatment course would be 5 days/wk for 1-10 weeks.
Early side effects
- Tiredness
- Fatigue
- Skin erythema
- Alopecia
- Mucositis (diarrhoea, dysuria) -
E.g - A common side effect of radiotherapy to the prostate region would be mucositis in the rectum called proctitis. This can lead to diarrhoea and the presence of blood in the stool.
Late side effects
- Skin pigmentation changes
- Pulmonary fibrosis
- Infertility
- Secondary cancers
- Constrictive Pericarditis -
Delayed constrictive pericarditis after radiotherapy for thoracic malignancies is well described, secondary to radiation-induced fibrosis of the pericardium. Constrictive pericarditis initially presents with features of right heart failure (such as a raised jugular venous pressure) as the right ventricle is less muscular and is first affected. A pericardial rub may be present as a result of the myocardium coming up against the edges of a tightened pericardium.
Radiotherapy is an important form of therapy for cancer and accounts for 50% of all treatment regimens. There are many side effects of radiotherapy and they are best characterised into early and late onset side effects
Squamous cell carcinoma often causes _____ as it secretes _____ not parathyroid hormone.
Hypercalcaemia
Parathryoid related peptide (PTHrp)
______ form the first-line combination chemotherapy regimen for Hodgkin’s lymphoma.
Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (abbreviated as ABVD)
The most effective treatment for SVCO is _____ .
Systemic treatment with chemotherapy
*The effects of this are most rapid in small cell lung cancers and lymphomas, which are highly chemo-sensitive tumours*
Percutaneous transcatheter insertion of a central venous stent - SVC stenting would be strongly considered in the palliative management of a patient with SVCO.
Evidence of SVCO can be elicited by _____ - where lifting the arms over the head for more than 1 minute will precipitate facial plethora (Swelling and redness) and cyanosis.
Pemberton’s test
Causes of raised AFP
Hepatocellular carcinoma
Liver metastasis
Neural tube defects
Germ cell tumours (e.g non-seminoma testicular tumour)
Cancers most likely to metastasise to the liver include ______, _____ and ____.
Colorectal (via the portal circulation which drains the gut)
breast
lung
_____ classification can be used to stage colorectal cancer:
Duke’s
A: limited to the bowel wall (i.e. not beyond the muscularis).
B: extending through the bowel wall (i.e. beyond the muscularis).
C: regional lymph node involvement.
D: distant metastases.
It is important to learn the Duke’s staging for examinations.
Patients with _____ in colon cancer benefit from ____ adjuvant chemotherapy.
Lymph node involvement (i.e TNM stage 3 or C stage in Duke’s)
post-operative
Current NHS screening programmes for colon cancer iinclude:
Faecal immunochemical test (FIT) every 2 years for men and women age 60-74.
If positive patients are referred for colonoscopy - this reduces the chances of death by 16%.
One of flexible sigmoidoscopy has now been discontinued.
_____ is not used as a diagnostic tool in colon cancer but can be used to monitor therapeutic response to interventions.
Carcinoembryonic antigen (CEA)
*however it is not always raised in patients and thus is not a reliable tool*
NOT used for diagnosis
For stage IV colon cancer disease (metastases): _____ chemotherapy may also be performed.
pre-operative
The staged colectomy and resection of metastatic disease is performed after pre-operative chemotherapy.
Peutz-Jeghers syndrome predisposes to colon cancer and is caused by a mutation in the ____ gene and has an _____ inheritance pattern.
STK11
autosomal dominant
Patients typically present in their teens with mucocutaneous pigmentaiton and hamartomatous polyps.
Note that the risk of neoplastic transformation of hamartomatous polyps is low, but many polyps are present so patients are at increased risk of developing colorectal cancer. They are managed with regular endoscopic surveillance.
Opiate naïve patients who are commenced on strong opioids such as Morphine will invariably experience nausea and constipation. They must therefore be started on ______.
Regular Senna and as-required Cyclizine
Although nausea is often transient, constipation persists due to reduced intestinal peristalsis. Therefore regular pro-kinetic laxatives such as Senna should be prescribed, whereas Cyclizine should be prescribed on an as-required basis.
Which opiate can be prescribed in patients with renal failure who cannot take morphine?
Alfentanyl
What type of cancer is the most common cause of death in the male population?
Lung cancer
Lung cancer is most common cause of cancer deaths in the male population account for 23%. However, it is the second most common form of cancer overall, accounting for 14% of all cancer cases in 2014.
_____ is the opiate of choice for patients with renal impairment, and therefore the most appropriate for this patient due to their significant diabetic nephropathy.
Oxycodone
According to NICE, a total daily dose of 20-30 mg of oral Morphine is safe and effective.
Oxycodone is approximately 1.5 times stronger than Morphine. Hence this regimen represents about 23 mg of oral Morphine, which is likely to be safe and effective.
It would also be necessary to prescribe as-required immediate release Oxycodone for any breakthrough pain (pain not controlled by regular opioids). This is stipulated as 1/6th the total daily opioid dose. In this case, 2.5 mg of Oxycodone is the right dose to prescribe for breakthrough pain.
What is the most important initial pharmacotherapy for patients suffering with symptoms of SVCO?
IV Dexamethasone (8mg BD)
- can be administered to reduce swelling and therefore the pressure on the SVC.
There is a diverse range of causes for confusion in oncology patients:
Metabolic disturbance (hypoglycaemia, hypercalcaemia)
Infection (pneumonia, UTI)
Metastatic spread to the brain
Anaemia
Intense pain
Side effects of pain medication
Common clinical features of head and neck cancers include:
Dysphagia
Odynophagia
Dysphonia
ALARM symptoms (tiredness, unexplained weight loss, loss of appetite)
Lymphadenopathy
Airway compromise (stridor)
Bad breath (halitosis)
Focal neurology (VII cranial nerve palsy)
In anybody that is immunosuppressed (e.g. taking azathioprine for Crohn’s or rheumatoid arthritis, recent chemotherapy or acute leukaemia), if they present with a sore throat, _____ must be excluded using an ____. This is true even if examination is normal.
neutropenia
urgent full blood count (FBC)
Morphine administered subcutaneously is _____ of oral Morphine
twice the strength
Signs of Hypercalcaemia in malignancy:
polyuria
polydipsia
constipation
confusion
Squamous cell carcinoma is the most likely malignancy as this is associated with paraneoplastic hyperparathyroidism (PTHrP). Additionally, squamous cell cancer is also associated with HPOA affecting the hands and feet.
*Important to remember though that HPOA can be caused by ALL types of lung cancer*
The WHO performance status classification categorises patients as:
0: able to carry out all normal activity without restriction
1: restricted in strenuous activity but ambulatory and able to carry out light work
2: ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
3: symptomatic and in a chair or in bed for greater than 50% of the day but not bedridden
4: completely disabled; cannot carry out any self-care; totally confined to bed or chair.
Medications for respiratory tract secretions in palliative patients
Hyoscine hydrobromide - Crosses BBB and thus can cause sedation but also act as an anti-emetic.
Hyoscine butylbromide - does not cross BBB
Glycopyrronium
General Side Effects of Chemotherapy?
Bone Marrow Suppression
Teratogenicity
GIT epithelium damage
Constipation
Hair loss (alopecia)
Fertility damage
Extravasation
Anaphylaxis
Drugs that cause specific side effects in chemotherapy?
Peripheral neuropathy (Platinum agents - Cisplatin/Carboplatin)
Cardiomyopathy (Anthracyclines - Doxrubicin/Daunorubicin / Herceptin)
Haemorrhagic cystitis - Cyclophosphamide
Endometrial Cancer - Tamoxifen
Lung Fibrosis (pneumonitis/ILD) - Bleomycin
Ototoxicity - Cisplatin
In a patient in which you suspect cancer, which blood result could would be a red flag?
Thrombocytosis (increased platelet count)
*remember cancer is pro-thrombotic*
What is the difference between acute and chronic leukaemia?
Acute: abnormal differentiation of bone marrow precursor cells
vs.
Chronic: Abnormal proliferation of mature malignant cells (for example - mitosis of monocytes becomes out of control)
What is the difference between myeloid and lymphocytic leukaemia?
Myeloid is a cancer of the myeloid progenitor cell which goes on to form cells such as erythrocytes/neutrophils etc.
vs.
Lymphocytic affects the lymphoid progenitor cell and thus cells such as B/T/NK cells (i.e the adaptive immune response)
What is the most commone leukaemia in adults?
Acute myeloid leukaemia - AML
*It is associated with myelodysplastic syndromes*
Clinical Presentation of AML?
It typically presents with symptoms of bone marrow failure:
Anaemia
Bleeding
Infections
and signs of infiltration, including:
hepatomegaly
splenomegaly
gum hypertrophy
How do you make a diagnosis of AML?
Blood tests commonly show Leukocytosis (raised WBCs) but white cells can sometimes be normal or low.
For this reason, diagnosis is dependent on bone marrow biopsy, as well as other molecular analyses.
Characteristic biopsy findings include Auer rods
Bone marrow biopsy of a patient suffering from AML will show which characterisitc finding?
Auer Rods
*Auer rods are red needlelike crystals that contain peroxidase (arrows) and are an occasional but highly specific finding for a myeloid neoplastic disorder*
The picture attached below indicates a cytoplasmic characteristic that indicates which cancer?
Auer Rods
Acute Myeloid Leukaemia
AML is usually treated with which two modalities?
Chemotherapy
Bone Marrow Transplantation
Prognosis of AML?
Without treatment: 2 months
With treatment: 20% 3-year survival rate
What is the most common cancer of childhood?
Acute Lymphocytic Leukaemia (ALL)
Clinical Presentation of ALL?
Common presentations include symptoms caused by marrow failure:
symptoms of anaemia including fatigue
abnormal bleeding/bruising caused by low platelets
infections caused by low white cells.
Symptoms may also be caused by organ infiltration:
Bone pain
Hepatosplenomegaly
Clinical Signs include:
Painless lymphadenopathy
Hepatosplenomegaly
CNS involvement (e.g. cranial nerve palsies, meningism)
Testicular infiltration (resulting in painless unilateral testicular enlargement).
How is a diagnosis of ALL made?
Blood results show leukocytosis and blast cells (too many lymphocytic progenitor cells - blast cells refer to any type of progenitor stem cell) on blood film and bone marrow analysis
Management of ALL?
Chemotherapy
Prognosis of ALL?
Children have a cure rate of about 70-90%
CML is most common in ____ patients, with males slightly more affected.
It is classically associated with the _____ chromosome.
Middle-aged (think ryan murphy - male middle aged)
Philadelphia
CML usually presents with _____.
Weight loss
Tiredness
Fever
Sweating
Common signs include:
Massive splenomegaly (>75%)
Bleeding (due to thrombocytopenia)
Gout
How do you make a diagnosis of CML?
Blood tests commonly show leukocytosis, in particular raised myeloid cells which include: neutrophils, monocytes, basophils, and eosinophils. Bone marrow analysis shows similar findings
Management of CML?
Chemotherapy
Prognosis of CML?
Median survival is 5-6 years.
CLL is most common in ____ patients over the age of ___ . It is caused by the proliferation of functionally incompetent malignant ____ cells.
Male
60
B-cells
Clinical features of CLL?
CLL typically presents asymptomatically.
However, patients may present with:
Non-tender lymphadenopathy
Hepatosplenomegaly
B-symptoms (weight loss, night sweats, and fever).
Features of marrow failure (infection, anaemia, and bleeding) are less common than in the acute leukaemias.
Diagnosis of CLL?
The most common initial blood result is an incidental lymphocytosis.
Subsequent blood film shows smudge cells, which are cells damaged as they lack a cytoskeletal protein.
Flow cytometry is then used to measure particular markers expressed by the malignant cells. Other tests include immunophenotyping bone marrow biopsy.
A blood film of a patient suffering with CLL will show ____ cells.
Smudge Cells
- which are cells damaged as they lack a cytoskeletal protein.
Management of CLL?
Chemotherapy
Prognosis of CLL?
Rule of 1/3’s:
1/3 regress (dont progress)
1/3 progrees slowly
1/3 progress rapidly
A _____ test detects antibodies or complement proteins that are attached to red blood cells and is used to detect haemolytic anaemias.
Direct Coombs Test
G6PD is an ______ red-cell enzyme disorder which may present in the neonatal period with jaundice, or later in life with episodic intravascular haemolysis following exposure to oxidative stressors.
X-linked recessive
The blood film of a G6PD patient typically shows ____ and _____ , and the diagnostic test is a _____ assay.
Heinz bodies (think glucose in heinz ketchup)
bite cells (heinz makes you wanna bite)
G6PD enzyme
Medications for restlessness and confusion
Haloperidol
Levomepromazine (broad spectrum but can cause tiredness)
Midazolam
Medications for nausea and vomiting in palliative
Levomepromazine
Cyclizine
Haloperidol
Metoclopramide
Medications for breathlessness in palliative patients
May be a result of disease process (e.g. lung cancer, anaemia)
Therapeutic oxygen
Morphine
Midazolam (syringe driver) or Lorazepam (oral)
What four items may you wish to discuss during an advanced care planning (ACP) meeting with a patient and family?
Tumour lysis syndrome is a common oncological emergency. It is associated with rapid cell death on starting chemotherapy and is common in tumours which are rapidly proliferating. These are classically haematological malignancies such as leukaemia and lymphoma.
Clinical features
It results in an increase in serum _____, ____, _____ precipitating renal failure.
Common symptoms include nausea, vomiting and muscle pain.
Management
Management focuses on preventing this from occurring through giving prophylactic _____ and in some cases a recombinant urate oxidase, rasburicase. Good hydration should be maintained.
UPP
urate
potassium
phosphate
*and hypocalcaemia - n+v and muscle cramps i.e tetany*
Deposition of uric acid and calcium phosphate crystals in the renal tubules may lead to an AKI/acute renal failure, which is often exacerbated by concomitant intravascular volume depletion due to the shift of potassium/phosphate and nuclei acids into the extracellular space - overwhelming normal homeostatic mechanisms.
allopurinol
Tumour lysis syndrome occurs ___ days after chemotherapy whereas neutropenic sepsis is more likely to occur ___ days after chemotherapy.
A few days (around 3)
10 or more days
Tunour lysis syndrome is a condition which typically presents a few days after chemotherapy and is common for haematological malignancies, particularly non-Hodgkin lymphomas. The administration of chemotherapy can cause significant cell death in mitotically active tumours, resulting in the extravasation of intracellular contents such as nucleic acids into the circulation. These are then broken down into uric acid and phosphate. Uric acid can precipitate in renal tubules leading to an acute kidney injury, which may cause the anuria as reported by this patient. Raised phosphate levels sequester free Ca2+ ions in the bloodstream, leading to hypocalcaemia and its characteristic symptoms, such as tetany (cramps) and vomiting.
This man has significant risk factors for tumour lysis syndrome and combined with anuria means that he may have an acute kidney injury. The most appropriate management for this should be fluid resuscitation in the first instance, particularly given his hypotension.
Common classes of chemotherapeutics and their mechanism of action.
Anti-metabolites (ex. Methotrexate/ Gemcitabine)
- Inhibit DNA synthesis
Alkylating Agents (ex. Etoposide)
- Prevent uncoiling of DNA (ex. topoisomerase inhibitors)
- Non-classical alkylating agents (ex. cisplatin/carboplatin) interfere with DNA cross linking.
Vinca Alkaloids (ex. vincristine/vinblastine)
- Cell arrest by preventing microtubule formation
Anti-mitotic antibiotics (ex. non-anthracyline - Bleomycin)
- Intercalation - inhibiting DNA synthesis
- Membrane binding - Increased permeability and destruction
- Free radical formation - disruption of the DNA chain nd prevening mitosis alkylation - blocking DNA replication
Taxanes
- Spindle cell inhibition
Toxicity of chemotherapeutics is measured in severity by using the ______
Common Terminology Criteria for Adverse Events (CTCAE)
Grade 1 - mild symptoms from adverse event
to
Grade 5 - death from adverse event
Which chemotherapeutics require renal function monitoring?
“CIMP”
Platinum agents (ex. cisplatin)
Methotrexate
Ifosphamide (alkylating agent)
Capecitabine (pro-5U drug)
Cell Cycle independent Chemotherapeutics?
Platinum agents (cisplatin/carboplatin)
Alkylating agents (ex. doxorubecin)
*think metals*
Febrile Neutropenia can be defined as a temp > ____ and a neutrophil count < ____
38 degrees
0.5 ×109/L
A ____ score is used to determine risk of febrile neutropenia in cance patients.
A score of > ___ is considered low risk
MASCC (Multinational Association for Supportive Care in Cancer)
> 21
*YOU WANT A HIGH SCORE*
Management of Hypercalcaemia in cancer patients.
- Vigorous fluid rehydration (4L in 24hrs unless elderly and frail)
- Monitor for signs of fluid overload and electrolytes
- Recheck serum calcium before bisphosphonates
- Give bisphosphonates after 24 hrs of fluid rehydration:
1st line : Zoledronic acid (4mg IV)
Wait at least 5 days before further treatment as bisphosphonate action takes time.
2nd line: Pamidronate
- Haloperidol is anti-emetic of choice in hypercalcaemia
*Bisphosphonates inhibit osteoclast activity reducing calcium release* - importantly they may prevent a recurrence unlike fluid rehydration
- Use of RANK ligand inhibitors (Denosumab)
Management of metastatic spinal cord compression (MSCC):
Emergency management:
Urgent MRI (<24hrs)
Steroids: Dexamethasone 8mg BD PO (early in day as possible to help sleep) + PPI - to prevent gastric bleed
Pain Management (WHO pain ladder)
Catheterisation/Laxatives
Definitive management:
Surgery or radiotherapy (palliative)
Surgery only indicated if prognosis is > 6 months and/or singular lesion
Offer patients with vertebral involvement from myeloma or breast cancer bisphosphonates to reduce pain and the risk of vertebral fracture/collapse.
The EGFR cell signalling pathway is a target of many immunotherapies as it is involved in _____ and ______.
Cell proliferation
Inhibition of apoptosis and cell survival
Monoclonal antibodies work on the outside of the cell whereas Tyrosin Kinase inhibitors work on the ____.
Inside of the cell with various protein targets.
Olarparib is a ____ inhibitor used in the treatment of ____ positive ____ cancer. It is used primarily as a maintenance therapy following a platinum chemotherapy agent (ex. carboplatin)
PARP - inhibit DNA repair mechanisms
BRCA
Ovarian
PARP - poly adenosine diphosphate-ribose polymerase, a type of enzyme that helps repair DNA damage in cells
____ is a downstream cell signalling protein in the EGFR cascade that can be targeted in melanoma treatment. This treatment can be enhanced by dual immunotherapy by combining with a ____ inhibitor.
BRAF
MEK
*Takes cancer longer to overcome both cell signalling protein inhibtion*
Anti-____ and anti-____ antibodies target so called “immune checkpoint” proteins, thereby activating the immune system to recognise and destroy cancer cells. In the process, the immune system becomes less discriminate at targeting healthy cells within the body, leading to various autoimmune sequelae.
• CTLA4 - ipilimumab
• PD1/PD-L1 –nivolumab, pembrolizumab
https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/checkpoint-inhibitors
3 main types of radiotherapy:
- External Beam Radiotherapy or Teletherapy (ex. stereotactic)
- Brachytherapy (radioisotope is delivered directly to the tumour site itself via catheter etc) - “inside out radiotherapy”
- Targeted Radionucleotide therapy / systemic radiotherapy (ex. injected into bloodstream and finds tumour. Endocytosed and then emits gamma ray - iodine for thyroid tumours)
https://www.youtube.com/watch?v=6lqnMIwplcE
____ takes advantage of the differential DNA repair mechanisms between Normal and tumour cells to deliver staggered radiotherapy to tissues.
Fractionation
Hyperfractionation means more number of doses
Hypofractionation means less regular doses but of a higher intensity
Radiotherapy like chemotherapy is most effective in the ___ and ___ phases of the cells cycle
G2 (growth) and particularly M phase (dividing)
The _____ (RAD) is the traditional unit of radiotherapy and corresponds to the amount of radiation absorbed per unit mass of tissue
This modern unit is known as the _____ and corresponds to Joules absorbed per kg of tissue mass (J/kg).
Radiation absorbed dose
Gray unit (Gy)
Immunohistochemistry indicators of primary source of malignancy?
1st line screen:
Carcinoma - Cytokeratin (e.g AE 1/3 / Cam 5.2 / MNF116)
Lymphoma - CD45 / CD3(T-cells)/ CD20(B-cells)
Melanoma - Melan A / HMB45 / S100
If none of these 2nd line screen:
Germ cell tumour
Sarcoma
Mesothelioma - Calretinin/ CK5/6 /WT1
IHC can be used to establish subclassification of carcinoma.
Squamous markers - ______
Adenocarcinoma markers - ______
Neuroendocrine - ______
Squamous cell:
P63 and CK5/6
Adenocarcinoma:
CK7 and CK20
Neuroendocrine:
Synaptophysin/ Chromogranin A / Ki-67
Routine tests done for molecular analysis of tumours.
Breast cancer - ER /PR/ HER-2 / Oncotype Dx
Gastric Cancer - HER-2
Colorectal Cancer - KRAS/ NRAS / BRAF/ MMR
Lung Cancer - EGFR / ALK/ PDL-1/ ROS-1
Melanoma - BRAF
GIST - KIT / PGDFRA
General Biochemical effects of Cancer
____ cells with their optically clear nuclei are pathognomonic of papillary thyroid cancers
Orphan-Annie
Papillary thyroid carcinoma findings are Orphan Annie Eye nuclei and papillae often associated with Psammoma bodies
WHO pain ladder and examples
Management of a patient presenting with acute MSSC?
1) Thorough history and examination (including neurological and PR exam) to
identify neurological deficits.
2) Referral for imaging: whole spine MRI scan is the gold standard for suspected
metastatic spinal cord compression.
3) If spinal cord compression is suspected - commence high dose
Dexamethasone 16 mg stat then 8 mg BD until imaging complete.
Follow local policy for urgent investigation and a protein pump inhibitor (e.g.
Omeprazole or Lansoprazole) if needed.
4) If pain is not controlled by step 2 of analgesics, we would escalate to step 3 (strong opioids + non opioids). This means commencing the patient on an opioid preparation (preferably on M/R (modified release) opiate, given he was taking step 2
analgesia) and stopping codeine PRN.
Consider co-prescription of a laxative and / or an antiemetic.
Additional Screen:
- FBC (rule out infection and neutropenia)
- U+E’s and LFT’s before opiate
- Bone Scan
- Myeloma Screen
(Discussion points: timescale for requesting urgent imaging, within a week vs within
24 hours - depending on clinical scenario i.e Bladder/Bowel dysfunction)
Hodgkin Reed Sternburg cells express ___ in virtually all cells and ____ in the majority of Hodgkin lymphomas.
Remember Reed Sternburg cells can exist in other lymphomas and this is why they are now referred to as Hodgkin Reed Sternburg (HRS) cells solely when they are seen in Hidgkin’s lymphoma
CD 30
CD15
CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker
Hodgkin lymphomas are divided into classic Hodgkin lymphoma and _____ Hodgkin lymphoma (WHO).
The classic Hodgkin
lymphomas (95% of cases) are further subtyped into:
_____ (constitutes 60 - 80%), characterised by dense ____
bands dividing lymph nodes into nodules.
_____ (20% cases) and has prominent ____ infiltrate.
Lymphocyte- ____ .
Lymphocyte-rich.
The last two subtypes are rare.
Nodular lymphocyte predominant
Nodular sclerosis - collagenous bands dividing lymphocytes into nodules
Mixed cellularity - eosinophilic infiltrate
Lymphocyte - depleted
Lymphocyte-rich
Hodgkin lymphoma most commonly presents with ___ enlargement of lymph nodes in the ___ or the ____ area.
60% of cases present with
involvement of the mediastinum. One quarter of cases show retroperitoneal LAP.
Mediastinal mass detected either incidentally or for the investigation of respiratory symptoms (cough, SOB or chest pain / discomfort) is also common.
Pain at the site of involved lymph nodes with ____ is unusual but characteristic finding.
painless
neck or supraclavicular
alcohol intake
Name the common causes of microcytic/normocytic/macrocytic anaemia?
The clinical features of multiple myeloma can be remembered by the mnemonic CRAB HAI:
Hyper(C)alcaemia: this arises primarily due to increased osteoclast-mediated bone resorption.
(R)enal impairment: this occurs due to multiple factors e.g. light chain deposition in the kidneys and hypercalcaemia.
(A)naemia: note that due to marrow infiltration by the tumour other cytopenias can occur (e.g. thrombocytopenia and leukopenia).
(B)one pathology: osteolytic lesions are common. This can lead to pathological fractures and vertebral compression fractures.
(H)yperviscosity: this can present with headache, visual disturbances, and thrombosis.
(A)myloidosis (AL): this has multiple sequelae including e.g. cardiac failure and neuropathies.
(I)nfection: recurrent infection occurs secondary to leukopenia and immunoparesis (there is low levels of functional IgG).
Paraprotein = abnormal antibodies produced by the immune system (ex. usually abnormal IgG or IgA or free light chains antibodies) - accumulate in the blood or bone marrow or both
*Beware ____ infection (pneumonia) in patients with febrile neutropenia as can be life threatening.
Invasive Aspergillosis
Most common leukaemia is ____
CLL
Myeloproliferative Disorders are caused by ____
Overproduction of mature cells in the bone marrow - known as a disorder of high blood counts
Multiple myeloma can be defined as the malignant accumulation of _____ cells in the bone marrow
Plasma cells (B-Cells that make antibodies)
In multiple myeloma multiple lytic lesions in the skull is often referred to as “_____ skull”
Pepper Pot
_____ lymphoma is can be high grade (usually fast growing) or low grade Non Hodgkin’s Lymphoma.
Burkitts (this is how you spell it)
How would you investigate and diagnose hodgkin’s lymphoma?
Surgical or radiological biopsy
Remember staging using Ann Arbor system
Lymphoma is staged using the ___ system.
Ann Arbor (CT and PET)
Stage 1: Single site
Stage 2: One side of the diaphragm
Stage 3: Both sides of the diaphragm
Stage 4: Outside lymph nodes (i.e bone marrow)
Lymphoma management comprises of _____ .
Chemotherapy +/- Radiotherapy
What are the causes of nausea and vomiting in palliative patients?
TREATMENT
• Chemotherapy
• Radiotherapy especially brain and
GIT
• Opioids
• NSAIDs
• Antibiotics
• PHYSIOLOGICAL
• Constipation
• Gastric stasis/outlet obstruction
• Raised intra cranial pressure
• Bowel obstruction
• Hepatomegaly
• Cough
• METABOLIC
• Hypercalcaemia
• Hyponatraemia
• Liver failure
• Uraemia
• Hyperkalaemia
• Infection
- PSYCHOLOGICAL
- Anticipatory
- Anxiety
- Fear
- Fatigue
Important receptor targets in Nausea and Vomiting (palliative)
Vomiting Centre _____
Chemoceptor Trigger Zone ______
GIT _____
Vestibular Apparatus _____
Vomiting Centre - Cyclizine
Chemoreceptor Trigger Zone - Haloperidol and Ondansetron
GIT - Ondansetron
Vestibular apparatus - Cyclizine
Causes of Constipation
Management of Constipation
Non-Pharmacological
- Tailored to any reversible causes.
- Diet, fluid intake and mobility.
- Environmental factors should also be discussed e.g. correct posture; suitable and accessible toilet facilities (e.g. toilet seat raisers); allowing adequate time.
- Privacy and dignity.
- Changes to a persons’ care and regimen should be minimised in order to avoid constipation.
- Secondary to spinal cord compression: maintain a regular schedule for toileting. E.g. alternative day suppositories.
- Medications should be reviewed regularly to minimise constipation
- Related factors such as reduced mobility, reduced food intake, weakness and dehydration should be addressed where practical and appropriate.
How does a rectal exam help you decide on suppositories to give in constipation?
How to choose a laxative ?
Rectal – quicker result.
Oral – usually patient preference.
Stimulant – if reduced frequency of stool. (ex. domperidone / metaclopramide)
Softener – if hard stools.
Mixed – if both.
Trial and error, often patients describe a mixed picture.
Important Receptors in N+V
Cyclizine acts at ____
Domperidone and Metoclopramide _____
Haloperidol _____
Prochloperazine ____
Ondansetron ____
Levomepromazine ____
Cyclizine - Anti-histamine/ Anti-cholinergic
Domperidone / Metoclopramide /Haloperidol- Dopamine receptor antagonists - CTZ
Prochloperazine - mainly Dopamine antagonist but also acts at histamine and 5HT - Mainly Vestibular apparatus
Ondansetron - 5HT3 antagonist - Cerebral Cortex / CTZ / GIT
Levomepromazine - Most receptors (histamine 5HT dopamine etc)
*Domperidone doesn’t cross BBB and so doesn’t cause extrapyramidal side effects*
Remember: Vomiting centre is located in the medulla and so lies outside BBB, whereas CTZ is inside.
Non-pharmacological management of Nausea and Vomting
Cyclizine
Action:
Good for:
Side effects:
Anti-histamine Anti-muscarinic (Acts at all vomiting centres)
Central, Vestibular, Bowel Obstruction
Side effect - Urinary retention (thus not good in renal failure either) - antimuscurinic
Haloperidol
Action:
Side effects:
Good for:
Dopamine receptor antagonist - CTZ
Extrapyramidal
Renal Failure and chemical toxicity (drugs, metabolic such as hypercalcaemia etc)
Hyoscine
Action:
Side effects:
Good for:
Levomepromazine
Action:
Side effects:
Good for:
Sedating and anxiolytic
Prochlorperazine
Action:
Side effects:
Good for:
In Nausea and Vomiting which medications can be used for:
Chemical Toxicity (i.e metabolic - hypercalcaemia) and drugs ______
Motility Disorders ____
Bowel Obstruction _____
Raised ICP _____
Movement related vestibular ____
Post-op ____
Unknown____
Chemical Toxicity (i.e metabolic - hypercalcaemia) and drugs
Dopamine antagonists (i.e Haloperidol, Domperidone, Metoclopramide)
Motility Disorders (i.e gastric stasis)
prokinetics - Domperidone and Metoclopramide
Bowel Obstruction
Anticholinergic (ex. Hyoscine/Cyclizine) - NB avoid prokinetics!
Raised ICP
Cyclizine and Steroid
Movement related/vestibular
Anticholinergic or antihistamine - Cyclizine, Hyoscine, Prochlorperazine
Post-op
Ondansetron (5HT3 antagonist)
Unknown
Levomepromazine (though cyclizine often given in ‘just in case’ pack)
Opiates that can be used in renal compromise?
Oxycodone (Aim to avoid in SEVERE renal failure)
Fentanyl (useful for those with stable pain requiring strong opiates)
Alfentanil (if patient requires syringe driver as fentanyl is transdermal) - thus can be used to titrate to patients pain quickly unlike fentanyl.
