Medicine D Flashcards
What are tumour markers and what are the types?
Tumour markers are defined as ‘anything present in or produced by cancer or other cells of the body in response to cancer or certain benign conditions that provide information about a cancer, such as how aggressive it is, what kind of treatment it may respond to, or whether it is responding to treatment.’
Tumour markers are seen in many types of cancers. There are many proteins and substances that are produced in higher quantities by cancer cells compared to normal cells. There is an increasing use of genomic markers and non-genetic changes in tumour DNA.
There are different types of tumour markers such as circulating and tissue markers. Circulating markers are present in blood, urine, faeces, and other fluids. Applications for tumour markers include screening, diagnosis, prognosis, staging, treatment selection, monitoring, detecting residual disease and detecting re-lapse.
How should tumour markers be used clinically?
Tumour markers have a relatively low clinical sensitivity (true positives) and results may be within normal limits in patients with malignancy. They also have relatively low clinical specificity (true negatives) and are found in patients without cancer. Tumour markers should always be interpreted in the presence of biopsies and imaging. Generally, TMs are best used in post-treatment follow-up with serial measurements rather than one-off tests.
Describe screening with tumour markers
The aim of screening is to detect disease early and limit the spread which improves outcomes. Limitations of using tumour markers include false positives and false negatives (early disease). Examples of targeted screening in genetic-linked diseases include BRCA1 and BRCA2 in breast cancer.
Sensitivity: Positivity in the presence of disease
Specificity: Negativity in the absence of disease
The presence of tumour markers is poor for diagnosis and so doctors should avoid fishing for multiple tumour markers. If a tumour load is related to tumour markers, then they can be used for a survival estimate. For example, HCG and AFP are prognostic indicators in testicular teratoma. P53, E-cadherin, nm23H1 and MMP-2 used together to predict outcome of node-negative breast cancer.
How are tumour markers used in treatment and monitoring?
Some receptors are used in deciding treatment such as HER-2 for Herceptin and oestrogen receptors in tumour tissue suggests responsiveness to hormone therapy.
Monitoring is the most useful role for classical tumour markers. This requires a quantitative relationship between tumour burden and tumour marker levels. This enables the assessment of efficacy of treatment. The detection of drug/chemo resistance and response and can even be used to classify remission. This requires an elevated tumour marker level at baseline for height of cancer diagnosis.
How are tumour makers used after treatment has been initiated?
Pre-treatment level should be high enough for a fall to be monitored. Knowledge of half-life enables response to be monitored by decline in levels. Generally:
- No change = tumour marker > 50% of T0 value
- Improvement = <50% of T0 value
- Response = <10% T0 value
- Complete response = tumour marker within reference interval
Monitoring relapse is a useful function of tumour markers. There has to be a balance between cost-effectiveness and clinical need. Rate of rise post resection of primary can indicate metastases such as CEA. Quick rise in CEA could be liver/bone whereas slower rise may indicate brain/soft tissue/skin metastases.
What is tumour lysis syndrome?
This is massive necrosis of tumour cells during treatment with cytotoxic drugs. Biochemical features include hyperkalaemia, hyperuricaemia, hyperphosphatemia, hypocalcaemia (precipitated by phosphate released from cells), tachyarrhythmias, sudden cardiac death, increased LDH (cytoplasmic release) and acute renal failure.
This can be prevented through maintenance of adequate hydration, allopurinol (xanthine oxidase inhibitor to inhibit uric acid synthesis), monitoring fluids and electrolytes with quick replacement, if necessary, urinary alkalinisation and renal dialysis.
Name some classical tumour markers
AFP, hCG, S100, Sp1, CA125, CA15.3, inhibin A, CEA, CA19.9, PSA, Chromogranin A, NSE, Calcitonin, thyroglobulin, CA211 and NMP22.
How are tumour markers used in testicular/germ cell cancer?
Testicular cancer presents with diffuse testicular swelling, hardness, and pain. Markers include AFP (alpha fetoprotein) and hCG (Human chorionic gonadotrophin). These markers contribute to diagnosis, staging and prognosis. Post treatment they can be used for monitoring.
AFP can also be elevated by liver regeneration, hepatitis, benign liver disease and pregnancy
HCG can be raised by pregnancy
How are tumour markers used in ovarian cancer?
Consider measuring CA125 if persistent symptoms (abdominal distention, early satiety, pelvic/abdo pain, urinary urgency/frequency, and IBS). If CA125 is greater than 35 then a US abdo and pelvis should be done. A RMI (risk of malignancy index) should be calculated and referral to specialist MDT if over 250. Measure AFP and hCG in women under 40 and refer urgently of there are ascites or abdominal/pelvic masses.
CA125 can also be elevated by pregnancy, menstruation, endometriosis, benign ascites, acute hepatitis, chronic renal failure, heart failure, and pleural effusion. Other malignancies can also elevated CA125 such as breast, cervical, endometrial, hepatocellular, lung and pancreatic.
How are tumour markers used in breast cancer?
Tumour markers are considered mandatory for all patients because oestrogen and progesterone receptors measured to identify those who can be treated with endocrine therapy. HER/2 receptors measured to determine those who can be treated with Herceptin.
BRCA1 variations increase the risk of breast cancer. BRCA1 and BRCA2 mutations have up to 60% risk of developing breast cancer by age 90 and have an increased risk of ovarian cancer. BRCA1/2 gene mutations can be used to determine treatment.
CA15.3: This is increased in breast cancer, especially with distant metastases and thus sensitivity increases in more advanced diseases. It is rarely elevated in patients with local breast cancer. This is used for post-treatment monitoring. It can also be raised in benign and malignant disease of lung, GI tract, reproductive systems, and liver disease. It is a specialist test performed in gynaecology.
How are tumour markers used in colorectal cancer?
CEA (carcinoembryonic antigen) is used for monitoring treatment response and detecting recurrence. It is not used in diagnosis as it is not present in early disease. Other causes of elevation of CEA include IBS, jaundice, hepatitis, chronic renal failure, pleural inflammation, and smokers. Other malignancies can cause elevated CEA such as breast, gastric, lung, medullary thyroid carcinoma, mesothelioma, oesophageal and pancreatic.
How are tumour markers used in pancreatic cancer?
CA19.9 has a low sensitivity and specificity, so its use is limited in early diagnosis. Its main use is for monitoring treatment. It is also raised in gallbladder, bile duct and gastric carcinomas. CA19.9 is also known as sialyated Lewis antigen. It can be elevated in colorectal, oesophageal, and hepatocellular cancers. Benign conditions which can elevate CA19.9 include pancreatitis, cirrhosis and disease of bile ducts.
How are tumour markers used in prostate cancer?
Clinical presentation include frequency, urgency, nocturia, dysuria, acute retention, back pain, weight loss, anaemia, and prostate enlargement. PSA is used to help diagnosis, assess response to treatment and monitor. Other causes of PSA elevation include BPH, UTI, prostatitis, catheterisation, TURP, prostate biopsy and recent ejaculation. It is not elevated by other malignancies and samples should be taken before DRE and 6 weeks after invasive procedures.
Prostate cancer and BPH can possibly differentiated because malignant prostate cells produce more bound PSA and a low level of free in relation to total. High levels of free PSA indicate a normal prostate, BPH or prostatitis. However, there are controversies surrounding PSA.
How are tumour markers used in thyroid cancer?
Thyroid cancer: Thyroglobulin can be used to evaluate response to treatment and to look for recurrence.
Medullary thyroid cancer: Calcitonin can be used to aid diagnosis, treatment response, and assess recurrence
When are immunoglobulins used for tumour markers?
Immunoglobulins (SERUM and URINE) can be used for multiple myeloma and waldenström macroglobulinemia.
ß2 Microglobulin: This is used for multiple myeloma, CLL and some lymphomas. This can be used to determine prognosis and response to treatment. It is also present in Crohn’s and hepatitis.
What is the JAK2 gene mutation seen in?
This is seen in AML and most myeloproliferative neoplasms
Describe some functional tumour markers?
- Pituitary: Prolactin, ACTH, GH and TSH
- Parathyroid: PTH
- Adrenal Cortex: Aldosterone and cortisol
- Adrenal Medulla: Catecholamines and metabolites
- Ovary: Oestrogens and testosterone
- GI tract: Insulin, glucagon, VIP, Gastrin and 5HIAA
Summarise prolactinoma
This is a benign tumour of the pituitary gland and the most common type of pituitary tumour. Symptoms can be caused by pressure (headaches and visual disturbance) or by hyperprolactinaemia (amenorrhea, infertility, lactation, loss of libido, erectile dysfunction, infertility, low oestrogen and thus osteoporosis. Treatment is with cabergoline, bromocriptine and norprolac.
Summarise Cushing’s syndrome
This is increased cortisol, hypokalaemia metabolic alkalosis, and glucose intolerance. Investigations should include dexamethasone suppression test, 24hr UFC, midnight salivary cortisol, imaging, and inferior petrosal sinus sampling.
Summarise growth hormone excess
90% of cases of acromegaly are primary (benign pituitary tumour) with few cases caused by tumours of the lungs, pancreas and adrenal also influencing it. Rarely IGF secreting tumours may be the culprit. A single GH measurement is not useful. IGF-1 is the more sensitive test and a glucose tolerance test should be done as in normal patients GH suppresses whereas in acromegaly GH remains detectable.
What is Conn’s syndrome and how is it investigated?
Primary aldosteronism (Conn’s) is HTN (young age and resistant to medication) and hypokalaemia. Investigations should include renin, aldosterone, ARR to screen, saline infusion test to confirm and adrenal vein sampling to lateralise.
Describe pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma presents with a classic triad of headaches, palpitations, and sweating. Investigations should include plasma free metadrenalines or total fractionated urine metadrenalines.
When is PTHrP used clinically?
This is related to function to PTH (same N-terminal). It is involved in cell signalling during development and has important physiological roles in growth and development. It is reportedly secreted by some lung, breast, prostate tumours, and myeloma. Hypercalcaemia is sometimes the first sign of malignancy. PTHrP should only be used in highly specific situations.
PTH functions include increasing Ca resorption from bone, reduced calcium excretion in urine and reduced renal phosphate re-absorption.
Which gut tumours are hormonal?
Gut hormone tumours include islet cell tumours, insulinoma, gucagonoma, gastrinoma, and VIPoma. Fasting gut hormone profiles may be required and quickly sent to the lab.
Summarise carcinoid tumours
Carcinoid tumours arise from argentaffin cells located in the foregut, midgut and hindgut. These can be found in the bronchi, stomach, small intestine, appendix and rectum. They secrete serotonin and have also been found to secrete ACTH, histamine, dopamine, substance P, neurotensis, prostaglandins, and kallikrein. Possible features include episodic flushing, wheezing, diarrhoea, and right sided heart valve disease.
Carcinoid tumour markers include 24hr urine 5HIAA as levels are not elevated with other types of tumours. 5HIAA is produced as a breakdown product of serotonin. Sensitivity is 73% and specificity of 100%. However, the level of 5HIAA only becomes elevated when carcinoid tumours have metastasised to the liver, making the potential for a cure unrealistic.
5HIAA testing is useful to estimate the extent of disease and prognosis. There may be a false positive test with foods rich in serotonin such as bananas, walnuts, plantains, pineapple, pecans, Kiwi and avocados. Drugs such as acetaminophen, aspirin (salicylates), guaifenesin and L-dopa can also interfere.
Chromogranin A is considered as the best test for detecting carcinoid tumours, and for monitoring their activity. Elevated levels of CgA are found in 80-100% of patients with carcinoid tumours and used in diagnosis, assessment of treatment and evaluation of recurrence. A positive test result does not always indicate carcinoid tumours are present, because CgA levels can also be increased by neuroendocrine tumours (phaeochromocytoma).
What are the features of MEN 1?
Parathyroid, pancreatic islet cells, and pituitary tumours. Biochemical tests include fasting gut hormones (including gastrin), insulin/glucose, and pituitary hormones. There is a MEN1 gene
What are the features of MEN2A?
Medullary thyroid carcinoma, phaeochromocytoma, and hyperparathyroidism. The genes involved are RET proto-oncogenes. Possible biochemical tests include calcitonin (in known disease), CEA (staging), metadrenalines (plasma and urine), calcium, and PTH.
What are the features of MEN2B?
Medullary thyroid carcinoma, phaeochromocytoma, and marfanoid. The genes involved are RET proto-oncogene. Possible biochemical tests include calcitonin (in known disease), CEA (staging), and metadrenalines (plasma/urine).
How will a blood smear appear in normal health and malignancy?
A normal blood smear will contain normal neutrophils, lymphocytes, and RBCs. A bone marrow biopsy may be needed to confirm leukaemia. This may be a bone marrow aspirate which is smeared and stained, this can also be genetically tested, and antibody tested. The other option is bone marrow trephine which is where a sample of core is decalcified, sliced, and looked at histologically.
In haematological malignancy the abnormal cells proliferate in the bone marrow and/or other organs to replace normal cells and reduce elements of the bone marrow which causes abnormal blood counts.
What are the 5 main types of haematological malignancy?
- Leukaemia can be acute or chronic
- Lymphoma: Hodgkin lymphoma, high grade non-Hodgkin lymphoma and low-grade non-Hodgkin lymphoma
- Myeloma
- Myeloproliferative neoplasms
- Myelodysplastic syndromes
How does acute leukemia present?
- Acute myeloid leukaemia (AML)
- Acute lymphoblastic leukaemia (ALL)
Clinical features include fatigue, infection, bruising, bleeding, high white cell count, low Hb (anaemia), thrombocytopenia (low platelets) and low neutrophils (neutropenia). Pathophysiologically there is an accumulation of blasts at the expense of normal haemopoiesis.
Summarise acute myeloid leukaemia
Acute myeloid leukaemia has an incidence of 3/100000 and occurs mainly in the over 65s. It is associated with radiation, previous chemotherapy, congenital syndromes, and previous myelodysplastic syndrome. Features include tiredness, infection, and bleeding.
Treatment is with 3-4 cycles of combination chemotherapy or haemopoietic stem cell transplants for some patients. There is an over 50% long term survival rate in fit patients and 1-20% in less fit patients.
Describe acute lymphoblastic leukaemia
Acute lymphoblastic leukaemia (ALL): This accounts for 30% of childhood cancers (600 cases per year in the UK) and 20% of adult acute leukaemia. Symptoms and signs include tiredness, bruising, bleeding, thrombocytopenia, weight loss, abdominal pain, lymphadenopathy, and splenomegaly.
Treatment is with induction and consolidation therapy. HSCT or 2 years of maintenance therapy. There must be some CNS prophylaxis throughout as this can progress to the brain or relapse in the brain and spinal cord so intrathecal chemotherapy and possibly radiotherapy to the brain and spinal cord should be considered. There is a 90% 5 year survival rate in children and 40% in adults.
What is invasive aspergillosis?
This is a complication of prolonged neutropenia and is life threatening.
Describe chronic lymphocytic leukaemia
This is the most common leukaemia in the western world. There is a slow accumulation of CLL cells in the blood, bone marrow, lymph nodes, liver, and spleen. There is a failure of the normal immune system and thus abnormal immune reactions as low antibody levels. CLL usually responds to treatment, but relapse is inevitable and subsequent treatments are less effective.
CLL is the most common leukaemia at 1/10,000. Clinically a immunophenotyping blood test is used for diagnosis, and there should be careful monitoring in case of transformation into a high grade lymphoma. It can be asymptomatic or cause weight loss, night sweats, temperature, itching, bruising, abdominal pain, enlarged lymph nodes, and an enlarged spleen. The majority of patients are over 60.
Therapy is with chemotherapy and targeted therapies. 70% of patients will require treatment for their disease. Novel treatments include ibrutinib and venetoclax which blocks thyrosine kinase and BCL2 respectively to prevent lymphocyte proliferation. Asymptomatic CLL does not require treatment.
Describe chronic myeloid leukaemia
CML is commonly associated with the Philadelphia chromosome (95%) which is a translocation between chromosome 9 and 22. T(9;22)(q34;q11). Incidence is 1/100,000.
20-50% are asymptomatic and found incidentally on FBC but signs and symptoms can include splenomegaly and bony pain. Treatment is with Imatinib or other tyrosine kinase inhibitors. There is an over 90% 7-year survival rate. Some patients can present in a blast crisis which is transformation to acute leukaemia (ALL or AML).
What are myeloproliferative disorders?
This is the over-production of mature blood cells. This can be the overproduction of neutrophils (CML), RBCs (polycythaemia vera) or platelets (essential thrombocytosis). Idiopathic myelofibrosis results in low blood counts due to replacement of bone marrow with collagen so there is extramedullary haematopoiesis and hepatosplenomegaly. Treatment is with gentle chemotherapy and venesection.
What are myelodysplastic syndromes?
This occurs when there is ineffective clonal haematopoiesis. This causes abnormal blood counts (anaemia) and should be considered in patients with abnormal blood counts with no obvious explanation (macrocytic anaemia with normal haematinics). The RBCs will have a dysplastic morphology. There is a wide spectrum of severity, and treatment varies depending on this. It almost exclusively occurs in patients over 60.
What are the clinical features of myeloma and how is it treated?
Clinical features include anaemia and pancytopenia (caused by accumulation of malignant plasma cells in bone marrow – b-cell derived antibody producing cells), lytic bone lesions (pathological fractures and hypercalcaemia), monoclonal paraprotein (hyper viscosity and renal failure) through IgG or IgA or free light chains. Mnemonic CRAB: Calcium, Renal, Anaemia and Bone
Treatment is with induction combination chemotherapy and autologous stem-cell transplants in the first remission. The disease follows a chronic relapsing course with may be treated with immunomodulatory drugs and monoclonal antibodies.
Describe the clinical findings of Hodgkin’s lymphoma
Hodgkin Lymphoma: 3/100,000 per annum. Classical HL present with asymptomatic lumps and incidence spikes between ages 15-30 and 65+. 25% will have systemic symptoms. Lymphopenia and anaemia are often present in advanced disease. Symptoms of pruritis and intermittent fevers are associated with night sweats. B symptoms are drenching night sweats and weight loss of more than 10% in 6 months.
Describe the clinical features of non-Hodgkin’s lymphoma
High grade b cell non-Hodgkin’s lymphoma affects all ages and usually presents with systemic symptoms and large masses/features of organ infiltration. Low grade b cell non-Hodgkin’s lymphoma usually occurs in the over 50s and the presentation is usually painless widespread low-volume lymphadenopathy. Splenomegaly is common in advanced disease and asymmetry, or bulk disease may signify high-grade transformation.
How should lymphoma be investigated?
Investigations should include a biopsy of a representative node/organ involved and HIV serology for HL or high-grade NHL. These tests are diagnostic. Staging is with CT neck/chest/abdomen/pelvis and a PET-CT for HL/high grade NHL The staging system is called Ann Arbor system.
How should lymphoma be treated?
HL: Combination chemotherapy +/- radiotherapy
High grade NHL: Combination chemotherapy +/- radiotherapy
Low-grade NHL: Guided by symptoms/disease extent
Stem cell transplantation can be autologous (patient’s own cells) or allogenic (donor). Autologous can be curative (HL) or to extend remission in myeloma whereas allogenic is always done for curative intent and most commonly used in acute leukaemia. Mortality is between 10-40% depending on the clinical situation.
How should red cells on the FBC be interpreted?
Important aspects are low Hb (anaemia), high HCT +/- Hb (primary/secondary polycythaemia) and low Hb in context of pancytopenia or high WBC (malignancy). Anaemia in infants (>150) and 6 months (>114) have different limits. MCV is used to investigate the type of anaemia and a low MCH may indicate IDA or thalassaemia. MCHC is only important if considered hereditary spherocytosis.
How should the MCV on the FBC be interpreted?
The normal range is between 80-100 fL unless pregnant (>85) or an infant (74-84). Generally microcytic is <80, normocytic 80-100 and macrocytic is >100.
Microcytic anaemia is caused by IDA, thalassemia trait, anaemia of chronic disease (usually normocytic), lead poisoning, and sideroblastic anaemia.
Normocytic anaemia is caused by anaemia of chronic disease, renal failure (low EPO), acute bleeding, mixed deficiency, MDS, leukaemia, and sickle cell disease.
Macrocytic anaemia is caused by B12/folate deficiency, liver/alcohol, MDS (myelodysplastic syndrome), haemolysis, hypothyroidism, and some medications. Pernicious anaemia is an autoimmune condition affecting B12 absorption and thus macrocytic.
Ferritin is used to diagnose IDA and should be above 20. Older patients with an IDA should be referred under 2ww for bowel cancer.
Microcytic anaemia in pregnancy is usually IDA or thalassaemia trait. If thalassemia trait, then the partners DNA becomes very important. This is more common in patients from a Mediterranean background.
How will haemolysis present on FBC?
Haemolysis will present with macrocytic anaemia, abnormal bilirubin but normal LFTs. A Haptoglobin should be done to confirm as part of the haemolytic screen. This is an emergency and requires admission and steroids.
How should macrocytosis be investigated?
Macrocytosis should be investigated with B12/folate/LFTs/ GGT/TFTs/LDH/Haptoglobin/retics and direct antiglobin tests. There should also be a comprehensive drug history taken. If B12 deficient (due to malabsorption such as PA or pancytopenia) then give IM folic acid. If there is evidence of haemolysis start folic acid and call haematology and if above is normal then consider MDS and refer to haematology.
How will myeloma present on investigations?
Myeloma may present with a normocytic anaemia, hypercalcaemia, and raised total protein. Anti-paraprotein should be considered abnormal.
Summarise polycythemia
This is defined as persistently raised Haematocrit (HCT). In women this is >0.48 and in males >0.52. This is almost always secondary to another condition such as reduced plasma volume (dehydration and diuretics) and increased red cell mass (hypoxia increasing EPO as seen in smoking, apnoea and altitude or ectopic sources of EPO such as renal or cerebral malignancy).
Primary polycythaemia is diagnosed when secondary causes are excluded. This is an acquired genetic mutation seen in JAK2 mutation (95% of patients) It is normally associated with raised platelets and WBCs and there is a risk of arterial and venous clots. Acute treatment (especially if there is a clot) is venesection aiming for HCT <0.45. There is a small risk of transformation into acute leukaemia or myelofibrosis. The EPO is often suppressed as the bone marrow is producing inappropriate amounts of RBCs.
Summarise thrombocythemia
Elevated platelet count in which the majority are transient and the rest reactive. There should be an urgent referral to haematology of the platelet count is greater than 1000 or platelets between 600-1000 in association with thrombotic events, vascular compromise, or neurological symptoms. There is an increased risk of thrombosis in primary thrombocythemia. Secondary causes include infection, bleeding, IDA, inflammation, and cancer.
Summarise thrombocytopaenia
Thrombocytopaenia (low platelet count) is asymptomatic if platelets less than 50 but there is a risk of spontaneous haemorrhage when platelets less than 20. You must always question whether the case is isolated or part of pancytopenia. Causes include spurious (sample problems), reduced production (drugs, B12/folate, viral infection, aplastic anaemia, malignant marrow infiltration, leukaemia, MDS, and HIV infection), or increased destruction (ITP, hypersplenism, DIC, TTP, HUS or SLE).
Other causes include drugs such as Alcohol, Thiazides, Quinine, heparin, valproate, phenytoin, carbamazepine, and gold. Acute or chronic infections which can cause it include TB, EBV, VZV, HIV, Strep, Mycoplasma and Hep C. Pregnancy can cause it if there is gestational thrombocytopaenia or HELLP syndrome.
What are the causes of elevated white cell counts?
- Neutrophils: Differentials can include infection, inflammation, and cancer (Haem and non-haem)
- Lymphocytes: If chronic this is normally in keeping with CLL
- Blast cells: Think Acute leukaemia if the patient is not severely unwell such as sepsis where bone marrow dysfunction may be expected.
If an elevated WCC also presents with anaemia or thrombocytopaenia then think leukaemia or bone marrow infiltration.
How is neutropenia defined and what are the causes?
Neutropenia is commonly due to transient viral infection, benign ethnic neutropenia (Afro-Caribbean), autoimmune disease, splenomegaly, drug induced, B12/folate, MDS, lymphoma, leukaemia, and myeloma if there are low platelets. Drug causes include carbimazole, septrin, sulfasalazine and psychotropic drugs).
Mild = 1-1.5, moderate 0.5-1 and severe is less than 0.5. Investigations should include FBC, film, B12/folate, autoimmune screen, and viral screen.
What are the causes of lymphopenia?
Lymphopenia can be seen in old age, infection, Drugs (steroids and other immunosuppression), alcohol excess, autoimmune disease, and systemic illness. Less common causes include immunodeficiency, and lymphoproliferative disorders. Investigations should include an FBC, film, repeat FBC in 6 weeks, HIV, Hep B and C, autoimmune screen, and immunoglobulins.
What are the causes of eosinophilia?
Eosinophilia should be a concern if it is chronic or progressive (not intermittent). Majority of the causes are secondary such as parasites, inflammatory disease, or malignancy. Primary disease is a diagnosis of exclusion and should have an urgent haematology referral if there are cytopenia, rapid rising count or evidence of end organ damage.
What are the common side effects of cancer treatment?
Common side effects of cancer treatment include myelosuppression (neutrophils/platelets/ reduced Hb), GI toxicity (nausea/vomiting/diarrhoea and oral mucositis), alopecia (is especially caused by alkylating agents, anthracyclines, Taxanes, and etoposide), infertility (alkylating agents can cause spermatogenesis and thus men more than women), and teratogenicity.
Describe some specific toxicities associated with cancer treatment
Specific toxicities include:
Cardiomyopathy (Anthracyclines such as doxorubicin and epirubucin)
Nephrotoxicity (cisplatin may be irreversible damage)
Ototoxicity as seen in Cisplatin where high pitch hearing loss is most common.
Pulmonary fibrosis is seen in bleomycin, busuphan and carmistine.
Neurotoxicity (peripheral neuropathy) is caused by Vincristine, Taxanes and Cisplantin.
Haemorrhagic cystitis is caused by cyclophosphamide and Ifosfamide.
Secondary malignancies are more common with alkylating agents (AML) and Etoposide (AML).
What are the social consequences of cancer treatment?
Financial: Cancer survivors are 37% more likely to be unemployed than others.
Quality of life is often understood via the metrics of mobility, self-care, usual activities, pain, and anxiety/depression. This is the EQ5D score.
What are the long-term consequences of cancer treatment?
Rare: Severe symptoms caused by damage to the brachial plexus from an obsolete form of radiotherapy for breast cancer
Intermediate: Faecal incontinence, urinary incontinence, and sexual difficulties from radiotherapy or surgery for pelvic cancers
Common: Risk of cardiovascular disease, fatigue, and osteoporosis caused by chemotherapy or hormone treatments for breast and prostate cancer.
How can long-term outcomes be improved for cancer survivors?
Improving outcomes can be achieved by using appropriate doses of drugs for therapeutic index and thus reduced damage to normal tissues. Recognising toxicity earlier will also help reduce the long-term impact. At the end of therapy all patients should have a holistic needs assessment to anticipate problems and get ahead of them. Utilise charities and support systems.
Generally how is radiotherapy delivered?
This is a type of treatment using ionization radiation to control or kill the cancer cells. Radiotherapy is used for 60-70% of all patients diagnosed with cancer. Types of radiotherapy include external beam radiotherapy/Teletherapy, Brachytherapy and radionucleotide therapy. Treatment should be delivered so that the tumour will receive the maximal possible dose whilst the normal tissue receives a dose within tolerance limits.
What is external beam radiation?
External beam radiation therapy can be 2- or 3-dimensional, intensity modulated, image guided, intraoperative, stereotactic or particle beam/proton radiotherapy. Conventional 2d radiotherapy uses X-rays to localise the tumour whereas 3D uses CT/PET/MRI scans to create a 3D picture of the tumour and the surrounding anatomy. 3D has an improved precision accuracy and thus decreased normal tissue damage.
What is intensity modulated radiation therapy (IMRT)?
Intensity modulated radiation therapy (IMRT) is a 3D method whereby radiation is shaped to fit the exact shape of the tumour. The radiation is broken into beamlets of which the intensity can be subsequently adjusted. IMRT allows higher doses of radiation to be delivered to the tumour whilst preserving tissue around the tumour.
For patients treated with 3D or IMRT there will need to be frequent imaging of the tumour, bony anatomy, and implanted fiducial markers for daily set-up accuracy. This also allows the movement of tumours to be tracked.
What is stereotactic radiotherapy (SBRT)?
Stereotactic radiotherapy (SBRT) and stereotactic radiotherapy (SRS0) refers to stereotactic radiation treatments in 1-5 fractions on specialised linear accelerators. This uses sophisticated imaging; treatment planning and immobilisation techniques and respiratory gating may be necessary for motions management in lung tumours (inspiration and expiration). SBRT is used for the spine, lung, liver, brain, adrenals, and pancreas.
What is proton beam therapy?
Proton beam therapy is where protons deposit most of their energy at a given depth, minimizing risk to tissues beyond that point. This allows for highly specific targeting of tumours located near critical structures. It is most commonly used in paediatrics, CNS and intraocular malignancies.
What is intra-operative radiation therapy (IORT)?
Intra-operative radiation therapy (IORT) is delivers a concentrated dose of radiation therapy to a tumour bed during surgery. Advantages include decreased volume of tissue to pass through, increase of the effective dose, and it has been proven to be good for breast cancer.
What is brachytherapy?
Brachytherapy is where radioactive sources are implanted into the tumour or surrounding tissue such as 125I, 103Pd, 192Ir or 137Cs. The purpose is to deliver high doses of radiation to the desired target whilst minimising the dose to the surrounding tissue. Types ca be intracavitary implants, interstitial implants, or intra-operative implants.
What is systemic radiation therapy?
Systemic Radiation Therapy uses radiopharmaceuticals, given by injection or IV, that collect where the cancer is and deliver their radiation there to kill the cancer cells. There is highly specific targeting of radiation with radionucleotides that decay within the body in specific locations. This is seen in iodine-131 for thyroid tumours, radium-223 for bone metastases and radioactive beads used for liver cancer.
How does radiotherapy work?
Generally, radiation therapy works by damaging the DNA of cells and destroys their ability to reproduce. Both normal and cancer cells are affected by radiation, but cancer cells have generally impaired ability to repair their damage which leads to cell death. All tissues have a tolerance level, or maximum dose, beyond which irreparable damage may occur.
Fractionation, or dividing the total dose into small daily fractions over several weeks which takes advantage of differential repair abilities of normal and malignant tissues. Fractionation spares normal tissue through repair and repopulation while increasing damage to tumour cells through redistribution and reoxygenation.
What are the factors that affect radio-sensitivity?
Factors which affect radio-sensitivity include physical (LET and dose rate), chemical (increased oxygen, cytotoxic drugs, and sulfhydryl compounds), and biological status such as stage of mitosis.
How is the radiation dose calculated?
The absorbed dose is the quantity of radiation absorbed per unit mass of absorbing material. The RAD (Radiation absorbed dose) is the traditional basic unit. The modern unit is the Gray (Gy or cGy), and is defined as 1 J absorbed/Kg.
Who is included in the radiation oncology team?
The radiation oncology team include a clinical oncologist, medical physicist, planning radiographers and treatment radiographers. Radiotherapy may be used as a neoadjuvant, adjuvant or palliative measure.
What conditions is radiotherapy used for?
Radiation therapy is used for adjuvant/neoadjuvant therapy in breast, prostate, lung, ano-rectal, oesophagus, head/neck, brain, skin, gynaecological, lymphomas, bladder, and sarcoma. Most side effects occur at the end of a treatment course. Treatment course usually run over 5 days a week for up to 10 weeks.
Palliative radiotherapy is useful for spinal cord compression, vascular compression (superior vena cava syndrome), bronchial obstruction, GI bleeding, gynaecological bleeding, oesophageal obstruction, and bone pain.
What are the side effects of radiation?
Radiation side effects include breast swelling and skin erythema, nausea, vomiting, diarrhoea, cough, SOB, oesophageal irritation, taste alternation, dry mouth, mucositis, skin redness, hair loss, scalp redness, urinary frequency, vaginal irritation, impotence, and fatigue but all these symptoms are dependent on the site which is being radiated.
