Blue book Flashcards

Question

How is imaging used in screening of cancer?

Answer 1

The use of screening mammography to detect breast cancer is now well established in the UK but the use of other radiological screening examinations has not proved effective (e.g. CXR to assess people at high risk of lung cancers, transvaginal ultrasound for ovarian cancer).

Answer 2

based solely on the X-ray attenuation of the tissues. Section thicknesses of between 1 and 10 mm are used depending upon the application. Oral contrast medium may be administered to outline the gastro-intestinal tract. Intravenous contrast medium is used to delineate vascular structures and to demonstrate tumour enhancement (thus increasing lesion detection, particularly in the liver). The principal concern about CT is the dose of radiation involved - one additional cancer per 1000-2000 scans performed. Always consider pregnancy before requesting scans or X-rays for women of child-bearing age.

Answer 3

images of high soft tissue contrast in any cross-sectional plane. now the gold standard for imaging neurospinal, rectal, prostate and musculoskeletal tumours, and is used for staging some subtypes of head and neck cancer. Images can be reconstructed to examine a particular organ system, such as MR angiography of the cardiac vessels, or MR cholangiopancreatograms. Real-time MR is of increasing use in diagnostic work such as the assessment of breast masses. no known toxicity Most pacemakers electronically vulnerable to the effects. Metallic foreign bodies can also be a contraindication, prosthetic joints are sufficiently fixed in place so as not to be a problem. Most surgical manufacturers now try to use non-ferrous materials for this reason.

Answer 4

reflection of high-frequency sound waves at soft tissue interfaces generates the ultrasound image. no ionising radiation, is safe, widely available and inexpensive. Used for: detecting metastases in solid ‘visceral’ abdominal organs, specialist applications such as duplex and doppler ultrasound are used to assess tumour blood flow. This can contribute to the characterisation of some neoplastic masses. real-time guidance of biopsy and therapeutic interventional procedures. less reliable for the serial measurement of lesions for response.

Answer 5

Radioisotope-Iabelled pharmaceuticals are administered, and their distribution measured by γ-camera detection of emitted photons. Many isotopes are given intravenously, e.g. technetium (Tc99m DTPA) used for isotope glomerular filtration rate (GFR) whilst some are given orally, e.g. radioiodine. Bone scintography (bone scan) remains the principal investigation for detection of skeletal metastases.

Answer 6

detects high-energy photons emitted by short-lived radioisotopes chemically tethered to molecules such as glucose or somatostatin to form a tracer produces functional images differentiate malignant from benign pathologies, Limited availability usually merged with standard CT taken at the same time in order to map functional images to detailed anatomy. The isotopes used have a short half-life in order to minimize radiation exposure to patients. The distance between production facility and clinical centre is therefore critical and the costs of manufacture and delivery of these agents is high. FDG-18 PET-CT can identify otherwise occult metastases from some cancers. It is used in situations where radical treatment appears possible but has high mortality and/or morbidity.

Answer 7

Tumour markers are substances produced either by, or in response to, tumour, and are present in blood or other tissue fluids and can be quantified. A tumour marker should be both highly sensitive so that few people with the disease are missed and highly specific so that few people are falsely labeled as having the disease.

Answer 8

The sensitivity of a marker describes its ability to detect those with a certain disease. If 100 people have the disease and the marker is elevated in only 95, its sensitivity is 0.95.

Answer 9

The specificity of a marker describes its ability to accurately define those who are disease free. If in 100 disease-free people the marker is negative in only 90 (i.e. there are 10 false positives) the specificity of the test is 0.90.

Answer 10

Cell-surface glycoproteins - CEA, CA125, CA19.9 Oncofetal proteins - HCG, α-feto-protein (αFP) Enzymesn - Acid phosphatase, Alkaline phosphatase, Lactate dehydrogenase, Neurone¬ specific enolase, Intermediate metabolites, 5-hydroxyindoleacetic acid, Vanillyl mandelic acid. Hormones - Thyroglobulin, Antidiuretic hormone, Adrenocorticotrophic hormone. Immunoglobulins - Bence Jones Protein, Light Chains Nucleic acids Both DNA and RNA can be detected. These can be tumour specific (e.g. Philadelphia chromosome, oncogene mutations), or tissue-specific [e.g. the detection of tyrosinase expression (a melanocyte-specific gene) in blood]

Answer 11

Screening - only certain high-risk groups have been identified in whom screening can be justified Diagnosis - Most tumour markers are elevated in a broad spectrum of malignancies. Many are also elevated in benign conditions. helpful in some diagnostic situations. e.g PSA is highly tissue specific Very high levels of some tumour markers are more likely to be due to a particular malignancy, just as the specificity of any test can increase if the cutoff value is moved. Prognosis - The rate of decline of a tumour marker following surgery or other treatments has been shown to relate to prognosis and may influence subsequent management. Response - One of the most clinically useful features of tumour markers is their ability to indicate response to treatment. In a patient with an elevated tumour marker, a reduction in the level of that marker whilst receiving treatment is highly suggestive of a response. Relapse In a patient who has previously been demonstrated to be have high levels of markers when disease is active (‘marker positive’), subsequent increase in the level is highly suggestive of tumour relapse. However some cancers will not show a rise in marker levels at the point of relapse and therefore over-reliance on a persistently normal level is not advisable.

Answer 12

relatively expensive blood tests and are not substitutes for a careful history and examination. False positive results and the over diagnosis of quiescent tumours (e.g. low grade prostate cancer in the very elderly) can cause anxiety, inappropriate further investigation and harm.

Answer 13

A cell surface antigen also expressed in a variety of normal tissues. elevated in a wide variety of tumours but its common clinical use is in the setting of colorectal carcinoma. The occurrence and degree of elevation is related to the clinical stage (4% in Dukes' stage A, 65% with Dukes' stage D). 98% of normal non-smokers have levels less than 5ng/ml. Elevated levels are also more common in people who smoke, or have inflammatory bowel disease, hepatitis, pancreatitis or gastritis.

Answer 14

Used as a marker in ovarian carcinoma, and is an antigen that is expressed on the surface of ovarian cells. It is not perfect in sensitivity and specificity: An elevated serum level has been found in 1% of normal women, 6% with benign conditions (pregnancy, endometriosis and pelvic inflammatory disease) and 82% of women with ovarian carcinoma. A level greater than 200 U /ml was not found in normal women or those with benign conditions. As with most markers its elevation is not specific for one tumour. Serum levels are also elevated in pancreatic (59%), lung (32%), colorectal (21%) and breast cancer (12%), usually where these are disseminated to the abdominal cavity.

Answer 15

A glycoprotein produced by the normal foetal yolk sac, liver and intestines. It is undetectable in normal individuals after the first year of life. Its level is moderately elevated in hepatitis but high levels are also produced by hepatocellular carcinoma and cancers containing yolk sac elements (e.g. teratoma). High levels of αFP predict a poor prognosis in malignancy.

Answer 16

A glycoprotein consisting of two subunits. HCG is elevated in patients with gestational trophoblastic disease (hydatiform mole, choriocarcinoma). There is also a specific elevation of the β-subunit in patients with non-seminomatous testicular cancers and some with seminoma. It is also raised in pregnancy!

Answer 17

A protein produced by prostatic cells. Levels are raised in prostate cancers, but also with benign hypertrophy of the prostate – a near ubiquitous phenomenon as men age. The level may also be elevated by rectal examination, in prostatitis and in urinary tract infection. PSA lacks sufficient sensitivity and specificity to act as an accurate screening test alone, although it is commonly used as a screening tool despite the equivocal evidence. It is used in monitoring response to hormonal and cytotoxic treatments, and in surveillance after radical treatment.

Answer 18

Can be a measure of the paraproteinaemias (e.g. myeloma and Waldenstrom’s macroglobulinaemia) and occasionally non-Hodgkin’s lymphoma. They can be measured in the blood or their excretion can be measured as light chains in the urine (Bence-Jones protein), which occurs in 40-50% of all cases of myeloma.

Answer 19

Fine needle aspiration cytology Tru-cut needle biopsy – a piece of the tumour is sampled under local anaesthetic Incisional biopsy- a piece of the tumour is sampled at surgery Excisional biopsy- the whole of a mass is removed

Answer 20

Curative intent: 30% of patients curable by surgical resection. requires localised disease, Adequate margins of clearance to minimise the risk of local tumour recurrence. may use (neo)adjuvant radiotherapy or chemotherapy -reduce the risk of local recurrence and, in some cases, allow the use of less radical surgery. reduce bulk of residual disease: long term benefit. e.g. ovarian cancer - significantly improves survival. only likely to be of benefit if there is effective therapy for the residual tumour. Curative surgery for metastases: some situations where surgical cure of distant metastases is possible e.g. solitary lung metastases from sarcomas or localized liver metastases from colon cancer. systemic therapy is almost always required in addition to the resection Palliative surgery: when an improvement in quality of life is considered likely and the risk of harm / likely length of hospital stay are considered acceptable. e.g. pinning of pathological fractures Prevention of cancer: surgical intervention can prevent cancer e.g. colectomy in patients with familial adenomatous polyposis coli or bilateral mastectomy

Answer 21

'cytotoxic' agents used in the systemic management of cancer. eradicate occult cancer cells. 60-70 % of cancer patients will require chemotherapy as a part of the treatment of their disease. Hormonal and biological treatments can also play an important role. Patients usually do not die as a result of local recurrence in the primary organ but as a result of systemic spread of the disease.

Answer 22

wide variety of mechanisms. Most agents target DNA either directly or indirectly. preferentially toxic towards actively proliferating calls. Tumours which divide rapidly, with short doubling times, usually respond best to chemotherapy.

Answer 23

Neoadjuvant - Pre-operative treatment of an operable tumour to make the tumour smaller, to allow less radical surgery, while at the same time treating occult micro metastases. aims to increase cure rates. Primary - Initial chemotherapy for a tumour that is inoperable or of uncertain operability, to reduce tumour bulk. may increase cure rates. Adjuvant - following surgery. treats the occult microscopic metastases which lead to relapse increases cure rates. Palliative - alleviate symptoms and maybe prolong life. carefully balanced decision so that the patient’s quality of life is not made worse by the treatment. It may be justified to give second or third line chemotherapy if the disease remains chemo-sensitive Curative - real chance of a cure even if there is metastatic disease at presentation. use of more intensive treatment associated with greater toxicity. only in select tumours Prophylactic - Hormonal treatments may be given before overt malignancy appears. E.g. tamoxifen may be used for in-situ breast cancer before invasive carcinoma is recognised.

Answer 24

* Different classes of drugs have different actions and may kill more cancer cells together by imparting several sub-lethal cell injuries than the sum of the cells they can kill when given individually (‘synergism’). * There is less chance of drug-resistant malignant cells emerging. * When drugs with different sites of toxicity are combined, dose can be maintained for each drug. Single-agent chemotherapy may also be appropriate, especially in the palliative setting.

Answer 25

given cyclically to allow normal cells to recover from the toxicity of treatment. The cells usually affected by chemotherapy at standard doses are haematopoietic stem cells and the lining of the GI tract, producing low blood counts (‘myelosuppression’) and mucositis. Giving the treatment every 3-4 weeks allows these cells to recover. Theoretically any cycle of chemotherapy will only kill a proportion of the tumour cells. Therefore repeated cycles are required to get tumour clearance. no advantage in giving endless cycles of chemotherapy, as this does not prevent resistance emerging and increases toxicity; many treatments are maximally effective after a 6-month course.

Answer 26

Conventional doses of drugs are those known to be effective against the particular malignancy and which, in the majority of patients, cause tolerable side effects. Many of these treatments can be given in an out-patient setting. “High dose” treatments produce toxicity requiring specialized supportive care including bone marrow support with growth factors, or ‘rescue’ using the infusion of previously harvested blood stem cells or bone marrow. The toxicity of this treatment is justified only when long term survival or cure are possible, which is only the case in relatively few cancers, such as Hodgkins disease and Ewings Sarcoma.

Answer 27

The use of prolonged chemotherapy to maintain a remission has little demonstrated advantage in solid tumours, as resistant clones soon develop and toxicity increases. In childhood leukaemia 18 months maintenance chemotherapy following the induction of a complete remission is central to modern treatment.

Answer 28

Orally - advantage of freeing the patient from lengthy hospital visits and invasive procedures. doesn’t necessarily reduce toxicity. regular review is almost always still required. cyclophosphamide, etoposide, capecitabine and tamoxifen are available orally. Variations in the levels of drug circulating based upon whether and when the drug is taken can be problematic Systemically - Most given intravenously as bolus injection or short infusion. Some chemotherapy may be given as a continuous infusion via a central venous line, either peripherally placed or tunneled under the skin to reduce the chances of infection. Regionally • Intravesical. Chemotherapy is routinely given this way in the management of superficial bladder cancer. This has the advantage of producing high doses at the site of the tumour, with negligible systemic absorption and hence minimal systemic toxicity. • Intraperitoneal. Chemotherapy may be administered directly into the peritoneal cavity in the context of tumours that spread trans-coelomically (e.g. ovarian cancer). • Intra-arterial. Any tumour that has a well-defined blood supply is potentially suitable for intra-arterial chemotherapy (e.g. hepatic artery infusion for liver metastases). This allows higher doses to be delivered to the involved site and reduces systemic toxicity.

Answer 29

Body surface area (BSA): Routine cytotoxic chemotherapy doses are calculated according to the patient's body surface area. The most commonly used formula is that of DuBois and DuBois, Carboplatin, a commonly used chemotherapy drug, is the only one to have its dose calculated directly according to the renal function. Some of the newer drugs, such as the monoclonal antibody trastuzumab, are calculated on body weight alone.

Answer 30

Nausea/Vomiting - Most cause, which can normally be controlled to a tolerable level. Ondansetron used Myelosuppression - kills haematopoietic progenitor cells - leucopenia and thrombocytopenia after 10 -14 days. counts return after 3-4 weeks. infection with a count less than 0.5 x 109/1 is significant. Gastrointestinal common. Oral mucositis, Diarrhoea, Constipation, paralytic ileus can develop due to autonomic neuropathy after platinum agents or vinca alkaloids. Alopecia rapidly dividing cell population at the hair follicle. reversible. use of a cold cap which reduces Neurological - Peripheral neuropathies. platinum drugs (particularly cisplatin), taxanes, and vinca alkaloids. principally affecting sensory nerves, may recover partially over a period of months - Autonomic neuropathy. - Central neurological toxicity. rare (ifosfamide-induced encephalopathy and 5-FU induced cerebellar toxicity). - Ototoxicity. Cochlear damage rather than auditory nerve damage with cisplatin. permanent. Pre-existing high-tone hearing damage precludes the use of cisplatin. Genitourinary - Nephrotoxicity. cisplatin and ifosfamide. adequate renal function is required to reduce overall toxicity. - Bladder toxicity. Cyclophosphamide and ifosfamide cause haemorrhagic cystitis Cardiac Doxorubicin and paclitaxel are both associated with acute arrhythmias. 5-FU may cause coronary artery spasm and therefore induce cardiac ischaemia. Hepatic transient rise of liver enzymes Skin and soft tissue toxicity - Extravasation. - Palmar plantar erythema (Hand-foot syndrome). - Photosensitivity. use of high-factor sun blocks. - Pigmentation. Bleomycin leads to skin and nail pigmentation. It occurs in combination with pulmonary fibrosis Others • Myalgia and arthralgia. paclitaxel • Allergic reactions. paclitaxel and docetaxel are associated with frequent hypersensitivity reactions • Lethargy. General malaise and fatigue are common and frequently debilitating.

Answer 31

Second Malignancies - sub-lethal DNA damage that may induce a second malignancy. The most carcinogenic - alkylating agents and procarbazine. Fertility Most associated with a reduction in fertility. alkylating agents, render patients infertile at standard doses. Most patients who have high-dose treatments become infertile. Counselling of patients is required. considered for sperm storage. Pulmonary Long-term pulmonary damage from fibrosis induced by drugs such as bleomycin and busulphan. High-dose or prolonged administration of most alkylating agents is associated with pulmonary fibrosis or pneumonitis. Cardiac cardiac fibrosis - predictable and dose-dependent. Younger patients are more susceptible Psychological and social prolonged effect on the patient's psychology, adversely affecting quality of life. Employment, relationships, insurance, and social adaptation are also frequently compromised, particularly in young people.

Answer 32

Treatment related - transient fall in the leukocyte and platelet count. nadir at 10 to 12 days. Recovery over a similar period. Higher doses more profound fall and more sustained. carboplatin cause relatively more thrombocytopaenia. also seen with biological therapies Bone marrow infiltration - pancytopaenia. more common in haematological malignancies and breast, lung and prostate cancer. Successful anti-tumour therapy will lead to an improvement in the pancytopaenia. Para-neoplastic syndromes - pancytopenia or falls in single haematopoietic lineages. Other - Blood loss from a tumour can cause anaemia, usually iron deficient. Anaemia without iron deficiency can be due to chronic disease of any type. Anaemia due to repeated chemotherapy treatment is often macrocytic, but not megaloblastic. Other general medical causes also apply to these patients and should be included in the differential diagnosis.

Answer 33

A transient nadir in blood counts following chemotherapy can be observed. However, prolonged or excessive degrees of suppression require investigation to exclude alternative causes such as marrow infiltration. Full evaluation includes a blood film, measurement of haematinics, bone marrow aspirate and trephine

Answer 34

A haemoglobin level less than 10 g/dl may well impair quality of life and patients can potentially benefit from blood transfusion. The use of recombinant erythropoetin in preventing symptomatic anaemia can also be beneficial, and reduce risks of transfusion reactions and viral transmission.

Answer 35

* Platelet counts less than 10 x 109/L are associated with a significant risk of spontaneous bleeding such as intra cerebral haemorrhage, with a risk of irreversible disability. They are an urgent indication for platelet transfusion. * Platelet counts between 10 x 109/L and 20 x 109/L are frequently supported with platelet transfusion, particularly in the presence of other complications such as infection. * Platelet counts greater than 20 x 109/L, in the absence of spontaneous bleeding, do not routinely require platelet transfusion. Repeated administration of blood products such as platelets is associated with the development of specific antibodies to blood cells including platelets. This manifests as a failure to increase platelet counts immediately after transfusion. This suggests the need for single donor (rather than pooled) or HLA matched platelets.

Answer 36

Clinical signs of significant thrombocytopenia include petechial haemorrhage, spontaneous nose bleeds, corneal haemorrhage and haematuria. Conventional doses of chemotherapy rarely cause clinically important thrombocytopenia. The use of high dose chemotherapy is associated with prolonged thrombocytopenia requiring regular platelet transfusions.

Answer 37

urgent broad-spectrum intravenous antibiotics. may quickly lead to multi-organ failure associated with septic shock. warned about these potential hazards Any pyrexia following chemo requires immediate review (within the hour) Total white counts less than 1 x 109/L with an associated fever require immediate in-patient management with broad spectrum antibiotics. can present feeling non¬-specifically unwell. Severe infection with end-organ failure - supported with growth factors and admission to intensive care where appropriate. look for source - Extensive cultures of blood, urine, sputum, throat etc. and a chest X-ray are take. but broad-spectrum cover is required. Failure to respond to initial antibiotics within 48 hours requires a change to second-line broad-spectrum antibiotics. Persistent fever despite appropriate antibiotic treatment requires consideration of additional antifungal or antiviral agents. Atypical infections such as pneumocystis pneumonia (PCP) and systemic fungal or viral infections may occur. Asymptomatic neutropenia may be closely observed without the need for antibiotics.

Answer 38

Prophylactic antibiotics - not generally used but in certain conditions should be considered e.g. COPD Dose modifications - curative chemotherapy such as Hodgkin's disease and testicular cancer every effort is made to maintain dose intensity. palliative chemotherapy the balance will usually favour dose reduction. Colony stimulating factors - may enable dose intensity to be maintained.

Answer 39

Cells either gain mutations that promote cell growth or lose genes that control growth. Key molecules are cell surface growth factor receptors and their intracellular biochemical pathways, check point inhibitors controlling cell division in the nucleus and molecules involved in apoptosis and cell death in response to various insults to the cell. More recently, it has been shown that cancer cells can also develop mechanisms for subverting the host’s immune system, preventing their elimination by immune effector mechanisms. Recent cancer drugs have been molecules targeting these specific pathways. As such, they have proved different from classical cytotoxic drugs, with very different side effects

Answer 40

those arising within tissues under hormonal control of normal cellular proliferation or survival. These include cancers of the prostate, breast and endometrium (sex hormones), and lymphocytic malignancies such as lymphoma, leukaemia and myeloma (corticosteroids).

Answer 41

* To shrink primary tumours before (neo-adjuvant) or instead of surgery (primary medical therapy) * To prevent or delay the growth of micro metastases following surgery (adjuvant therapy) * To shrink established metastases and improve quality and duration of life (palliative therapy)

Answer 42

usually involve steroid hormones. Steroids interact with cytoplasmic protein receptors to form functional DNA transcription factors, affecting the transcription of multiple genes. - Removing the source of a growth-promoting hormone e. g. bilateral oophorectomy/bilateral orchidectomy - Hormone inhibitors drugs that block the binding of hormones to their receptors in tumour cells. The best known is tamoxifen that acts (in part) as an anti-oestrogen. - Increasing hormones Glucocorticoids in high concentration induce apoptosis in some malignant lymphoid cells. Hormone supplementation is used in certain sex-hormone sensitive cancers with the aim of inducing negative feedback loops. may give direct inhibition of tumour growth via acting as an agonist of the progesterone receptor, but also produce negative feedback on the pituitary/gonadal axis. These drugs may also stimulate the appetite and are widely used in palliative medicine for that reason.

Answer 43

In pre-menopausal women, permanent ovarian ablation may be induced by radiotherapy. reversible "medical castration" is achieved by long-acting LHRH analogues (e.g. goserelin, leuprorelin) which, by receptor down-regulation in the pituitary, block LH and FSH production and, in turn, gonadal hormone output. These techniques are unsuitable for postmenopausal women, for whom sex hormone production is mainly extra-gonadal, in fat and the adrenal glands. The rate-limiting step in oestrogen synthesis is the conversion of androstenedione to oestrone by the enzyme aromatase. In postmenopausal women, androstenedione is secreted by the adrenal and aromatized in other tissues including fat and liver. This step is the target for aromatase inhibitors. New potent, specific aromatase inhibitors (anastrozole, exemestane, letrozole) are highly effective in clinical trials with greater efficacy and less toxicities.

Answer 44

Steroidal anti-androgens (e.g. cyproterone acetate) have a dual action. In tumour cells they inhibit the androgen receptor, but in the hypothalamus they substitute for testosterone, so stimulate negative feedback inhibition with subsequent decrease in LHRH release. Non¬-steroidal anti-androgens (e.g. bicalutamide) inhibit testosterone in both tumour cells and hypothalamus, so feedback inhibition is lost and serum testosterone levels rise. "Maximum androgen blockade" describes the combination of a non-steroidal anti androgen with an LHRH analogue to prevent this effect and is used as a therapeutic strategy in prostate cancer.

Answer 45

certain sex-hormone sensitive cancers with the aim of inducing negative feedback loops (e.g. oestrogens to down-regulate hypothalamic LHRH in prostate cancer) or tachyphylaxis (down-regulation) of receptors (e.g. high-dose oestrogens in breast cancer).

Answer 46

curative potential - only if no distant metastatic spread. delivered as the sole treatment e.g. prostate cancer. commonly combined with chemotherapy to improve the efficacy of treatment neo-adjuvant - reduce the risk of local recurrence e.g.of rectal cancer adjuvant - reducing loco-regional recurrence, e.g. breast cancer. palliation of symptoms and/or to control cancer growth when cure is not possible.

Answer 47

photons/x-rays, electrons, radio-isotopes or protons. External beam radiotherapy using photons/x-rays is the most common form of radiotherapy used in the UK.

Answer 48

generated and delivered by a linear accelerator X-rays penetrate deep into body tissue whilst sparing the over-lying skin produce secondary electrons and free radicals which cause DNA damage to both cancer cells and normal cells Normal cells can often repair the DNA damage and therefore survive cancer cells commonly have defective DNA repair pathways and are unable to repair radiotherapy induced DNA damage balance of killing cancer cells without causing irreversible damage to the surrounding normal tissues The dose of radiation is expressed in the unit Gray. commonly delivered as a series of small doses called fractions rather than as a single large dose. The number of fractions and the dose (Gy) given in each fraction depends on the treatment intent. Radical/curative treatments require large doses of radiotherapy overall. The total dose is then divided into multiple small fractions

Answer 49

Palliative radiotherapy, which is primarily given to alleviate symptoms, is delivered in a smaller number of fractions and to a lower total dose. Commonly used palliative schedules are 8Gy in 1 fraction, 20Gy in 5 fractions or 30Gy in 10 fractions

Answer 50

* treatment issues, for example: the total dose, the total volume treated, dose per fraction and overall treatment time, * co-morbidities (such as diabetes and inflammatory bowel disease), smoking, * Intrinsic radio-sensitivity of the cancer cells (seminoma and Hodgkin's disease are highly radiosensitive and respond well to low doses of radiation whereas cancers such as a glioblastoma multiforme are relatively radio-resistant to even high doses of radiotherapy), tumour hypoxia, tumour re-population and additional treatment such as chemotherapy.

Answer 51

Chemotherapy given to patients during their radiotherapy treatment is called concurrent chemotherapy and is thought to act as a radiosensitiser, which means it increases the sensitivity of the cells to radiation. This improves the efficacy of the radiotherapy treatment without having to significantly increase the dose of radiotherapy. Concurrent chemoradiotherapy regimens are associated with increased radiation-related side effects, in addition to the expected side effects of the chemotherapy drugs.

Answer 52

The tumour is delineated on each CT slice it appears on, this is called the Gross tumour volume (GTV). A margin is then added for microscopic disease spread (the clinical target volume (CTV) - which may include adjacent nodal groups). further margin is added to allow for minor daily variations in patient and tumour position, this is called the planning target volume (PTV). A radiotherapy plan is then created that conforms to this shape, thereby treating the tumour whilst avoiding as much normal tissue as possible

Answer 53

develop during treatment, usually after the first 5-10 fractions. increase during treatment and hit a peak in the first few weeks after treatment. generally reversible but must be managed appropriately, t Acute side-effects of radiotherapy are due to damage of normal tissue and the ability of normal cells to repair the damage also explains why the acute side effects usually completely resolve once treatment has finished. Such side effects included a localised skin reaction, oral mucositis and diarrhoea.

Answer 54

Develop at least 3 months after radiotherapy and sometimes manifest years later. often irreversible and may worsen over time. difficult to treat and require multi-disciplinary management, including surgery. Long-term toxicity occurs as some of the damage to normal cells cannot be repaired and partly due to the development of fibrosis and blood vessel damage within the irradiated tissue. e.g. lung fibrosis, skin atrophy and infertility. Radiotherapy itself is carcinogenic and there is a risk of a second malignancy. The risk increases over the decades after treatment and depends on the treated volume and dose. for women receiving radiotherapy for breast cancer, there is an excess absolute risk from radiotherapy of 2 to 4 cases per 10,000 person years. The risk is significantly greater for younger patients treated for a good prognosis cancer. Radiotherapy is also teratogenic and therefore must be avoided in any woman who is pregnant.

Answer 55

radiation treatment where radiation sources are placed within or close to the tumour. It allows the delivery of a localised high radiation dose to a small tumour volume, increasing the chance of tumour control, whilst minimizing the dose to surrounding normal tissue. The commonest cancers to be treated with brachytherapy are prostate cancer, gynaecological cancers, oesophageal cancer and head and neck cancers.

Answer 56

* Intracavity: the radioactive material is placed inside a body cavity such as the uterus and cervix. * Interstitial: where the material is put into the target, such as the prostate.

Answer 57

A radioisotope is an unstable form of a chemical element, which emits radiation when it decays and is another method of radiation delivery. The most commonly used form is radioactive iodine, I-131, which is used in the management of the most common forms of thyroid cancer. The iodine is preferentially taken up by and concentrated in any remaining thyroid tissue, normal or malignant, where it emits radiation as it undergoes radioactive decay, ablating the thyroid cells. As there are few other tissues in the body that take up iodine this is a way to selectively deliver radiation. The patient will need to remain in the lead lined room until the level of radiation they are emitting is low enough to be safe to others, which is usually around four days.

Answer 58

* The subjective evaluation of life as a whole. * Patients' appraisal of and satisfaction with their current level of functioning compared with what they perceive to be possible or ideal. * Physical, mental and social well-being, not merely the absence of disease or infirmity (WHO).

Answer 59

1. Physical functioning. This includes performance of self-care activities, functional status, mobility, physical activities, and 'role activities' such as work or household responsibilities. 2. Disease and treatment-related symptoms. This includes specific symptoms from the disease such as pain, shortness of breath or side effects of drug therapy such as nausea, vomiting, hair loss. 3. Psychological functioning. Including emotional distress, anxiety or depression (that may be secondary to the disease). 4. Social functioning. For example family interactions, time with friends, recreation activities. ``` 5. Others. Additional considerations in the evaluation of QL may include: Spiritual or existential concerns. Cognitive function. Sexual functioning and body image. Satisfaction with health care. ```

Answer 60

Tumours should ideally: • Be curable when detected early in the majority of the patients. • Be relatively common. • Have a long pre-invasive or non-metastatic stage. • Be able to be detected by relatively simple tests. • Be distinct from benign lesions.

Answer 61

* Be able to detect cancer at an early enough stage to implement effective treatment. * Be sensitive – i.e. be able to distinguish tumours clearly and give a low false negative value (i.e. not miss actual cases). * Be specific – i.e. would not give false positive results * Be well tolerated, hence improving compliance. * Be easy to administer or perform. * Be inexpensive. * Be well publicised in order to ensure high uptake amongst the target population.

Answer 62

* Reduction of mortality by detecting early disease that is curable. * Less radical treatment hence reducing morbidity. * Saving on health service resources by increased cure rates. * Reassurance given by a negative test.

Answer 63

* Increased length of anxiety and morbidity if no effective intervention is possible. * The over-investigation of false positive cases with associated morbidity. * Over-treatment of borderline cases that do not require treatment. * False reassurance from a false negative result. * Possible harmful effects of the screening test. * Cost of screening a large population.

Answer 64

* Limit the screening to “at-risk” populations. This improves the overall sensitivity and specificity. It also often allows more effective targeting of the test which increases compliance. The resource implications are also favourable if an at-risk group and their characteristics can be identified. * Develop an effective infra-structure, for example through primary health care teams, support groups and through work places to increase awareness and uptake of at-risk populations.

Answer 65

This is the most effective screening programme to date. All women aged between 25 and 64 are offered screening. Women aged 25 to 49 are invited for “cervical smears” (cytological assessment of collected specimens) every three years. After that they are invited every five years. This is particularly successful because of the relatively long pre-¬invasive period during which early detection can occur, and for which an effective treatment can be offered. Issues: Screening of both at-risk patients (that is those with a strong family history) and the general population, with CA125 and trans-vaginal ultrasound, is being studied.

Answer 66

Regular mammography is offered to all women between the ages of 50 and 70 every 3 years. The ability of mammography to reduce mortality remains controversial. Screening for younger patients who are at increased risk, such as those with a family history should be considered as part of a package of care, including screening if appropriate, after referral to a breast cancer service.

Answer 67

men and women are offered bowel screening, using faecal occult blood (FOB), every two years from 60 to 69. The English programme is being extended to 74; older patients can request a screening kit. At risk patients, such as those with ulcerative colitis, a strong family history or a previous primary tumour should be screened within their existing management plan including regular colonoscopies.

Answer 68

There is no organised screening programme for prostate cancer but an informed choice programme, ‘Prostate Cancer Risk Management’ has been introduced. This provides information for patients about the pros and cons of having a PSA test performed. Men are often diagnosed with prostate cancer later in life. Many of these tumours would never progress during the remainder of the man’s natural life and the majority of men diagnosed would die with, rather than of, their prostate cancer. There is therefore a significant risk of over-treatment with the associated risks and harms.

Answer 69

* Provides relief from pain and other distressing symptoms * Integrates physical, psychological, social and spiritual care * Affirms life and regards dying as a normal process * Neither hastens nor postpones death * Helps patients live as actively as possible until death * Offers support to help the family/carers during the patient’s illness and into bereavement.

Answer 70

A diagnosis of the cause of the symptom is an essential step towards effective symptom management. Symptoms may be caused by: • The disease itself • The treatment • A concurrent disorder Any reversible causes should be identified and treated if possible. Good palliation may include treatments to modify the disease itself, as well as medicines to control symptoms. pharmacological and non-pharmacological treatments. Attention to detail is paramount; symptoms and their cause may change daily.

Answer 71

a voluntary process of discussion and review to help an individual who has capacity to anticipate how their condition may affect them in the future and, if they wish, set on record choices about their care and treatment

Answer 72

* Advance statement of wishes to inform subsequent best interest judgments * Advance decisions to refuse treatment which are legally binding if valid and applicable * Appointment of Lasting Powers of Attorney for ‘Health and Welfare’ and/or ‘Property and Affairs’.

Answer 73

what the patient says hurts”. Pain is a total personal experience with physical, psychological, social and spiritual dimensions.

Answer 74

* Onset & duration * Site & radiation * Character * Temporal factors * Exacerbating factors * Relieving factors * Severity * Associated symptoms * Effects on sleep, work, mood * Current treatment * Treatments tried and results * Understanding of illness * Expectations

Answer 75

occurs in about 80% of patients ``` Bone pain visceral pain Headache/ICP neuropathic infection ```

Answer 76

Features - Either a dull ache over a large area or well localised tenderness over the bone. Often worse on weight bearing or with movement. Treatment NSAIDS (e.g. diclofenac 50mg tds), radiotherapy and bisphosphonates (e.g. pamidronate infusion).

Answer 77

Features - Dull, deep-seated, poorly localised pain. There may be tenderness over a particular organ (e.g. liver). Some visceral pain is spasmodic such as bladder spasm or bowel colic. Treatment For constant dull visceral pains follow the analgesic ladder. Pain caused by visceral stretch such as liver capsule pain can be treated by NSAIDS or corticosteroids to reduce inflammation. Colic pain responds to anticholinergic drugs such as subcutaneous hyoscine butylbromide for bowel colic and oral oxybutynin for bladder spasm.

Answer 78

Features This is a dull, oppressive pain usually worse on waking, coughing, sneezing and may be associated with nausea and vomiting. Treatment Corticosteroids to reduce the oedema (e.g.16mg po dexamethasone daily, reduced to lowest effective dose), NSAIDs and paracetamol.

Answer 79

Features - Pain in an area of abnormal sensation. It may be localised to specific dermatomes or over a wider, less defined area. There may be altered sensation in the area such as numbness or hyperaesthesia and autonomic changes such as pallor or sweating. The patient may describe the pain as ‘pins and needles’ or burning. Treatment Antidepressants (amitriptyline 10-75 mg nocte) and anticonvulsants (gabapentin 100-1200mg tds, pregablin 25-300 mg bd ). Compression of a nerve may be helped by corticosteroids.

Answer 80

Step 1 - Paracetamol Step 2 - Weak opioid e.g. Codeine plus paracetamol (eg Co-codamol) Step 3 - Strong opioids e.g. Morphine/ diamorphine ``` NSAIDs may be used at any step Other adjuvant drugs include; Antiepileptics Antidepressants Corticosteroids ```

Answer 81

* Constipation is almost universal. Always prescribe a laxative e.g. co-danthramer. * Nausea and vomiting occur in about one third of patients starting strong opioids but usually settles within a few days. Prescribe a p.r.n. antiemetic (e.g. haloperidol) and consider a regular antiemetic if the patient is already nauseated or has had sickness in the past. * Drowsiness may occur when starting or changing the dose of opioid. This usually improves within 48 hours. Excessive sedation may indicate excessive dosing or co-morbidity e.g. renal impairment. * Confusion and visual hallucinations are rare if the correct dose is given. Check the dose and renal function and consider an alternative opioid if confusion persists. * Respiratory depression is rare if the opioid is titrated correctly. * Psychological dependence and addiction are common fears amongst patients but are rarely a problem in clinical practice.

Answer 82

* Normal / immediate release tablets and liquid – would be expected to be effective after 20-30 minutes and to last up to 4 hours, e.g. oramorph liquid or sevredol tablets * Modified /slow release tablets, granules, or capsules – would be expected to last up to 12 hours, e.g. Morphine Sulphate Tablets (MST), Zomorph capsules

Answer 83

If the patient has been on maximum strength co-codamol then MST 20mg bd is usually appropriate. Elderly or frail patients may require lower starting doses. Patients with renal failure will accumulate morphine metabolites and the dose and frequency should be reduced or a non-renally excreted alternative considered (e.g. fentanyl).

Answer 84

Titrate dose upwards by 30-50% increments to relieve pain or until unacceptable adverse effects occur. Always check the pain is opioid sensitive.

Answer 85

All patients on modified release morphine should have normal release morphine available p.r.n. for breakthrough pain, i.e. 1/6th of their total 24 hour morphine dose

Answer 86

Parenteral diamorphine is 3 times more potent than oral morphine. It is highly soluble in small volumes of diluent. Parenteral morphine sulphate is 2 times more potent than oral morphine. The total 24 hour subcutaneous continuous infusion diamorphine dose should be one third of the total 24 hour oral morphine dose e.g. a patient on 30 mg oral morphine bd. would require approximately 20 mg diamorphine SC over 24-hours (60 mg in 24-hours divided by 3) or 30 mg morphine sulphate SC over 24-hours (60 mg divided by 2).

Answer 87

Fentanyl transdermal patches have a duration of action of 72 hours. They are mainly suitable for patients with severe chronic pain already stabilised on other opioids. Transdermal buprenorphine patches are also available.

Answer 88

Oxycodone has similar pharmacological properties to morphine and is a useful second line strong (step 3) opioid for patients who have not tolerated morphine. It is available as an immediate release (oxynorm) and slow release preparation (oxycontin).

Answer 89

Other strong opioids available include alfentanil, methadone and different preparations of fentanyl (sublingual, buccal and nasal).

Answer 90

Palliative radiotherapy e.g. for bone pain Palliative chemotherapy e.g. for tumour masses compressing viscera or nerves Surgery e.g. intramedullary nail for pain from a femoral metastasis Anaesthetic and neurosurgical interventions e.g. paravertebral nerve block Psychological interventions e.g. cognitive behavioral therapy Transcutaneous Electrical Nerve Stimulation (TENS) Complementary therapies e.g. aromatherapy

Answer 91

Mouth problems - Dry mouth (xerostomia) can result from reduced intake of oral fluids and many drugs used in palliative care (e.g. antiemetics, antidepressants). Radiotherapy to the head and neck may cause a severe dry mouth. A dry mouth can result in loss of taste, anorexia, halitosis, dysphagia and oral infection. Oral thrush (candidosis) may be asymptomatic or cause altered taste, soreness or pain. Anorexia - try to elicit any reversible cause such as oral thrush, nausea, pain, constipation, depression. Ensure food is nicely presented and small portions are offered. The family may need educating not to pressurise the patient to eat and about food preparation. Nausea and vomiting - An identifiable cause found in one third of patients. Multiple causes will be found in another third and in the remaining third no identifiable cause will be found. identify the most suitable antiemetic. Parenteral antiemetics, given regularly, are often required for severe nausea or vomiting (see syringe drivers).

Answer 92

Treat with systemic antifungals (fluconazole 50mg o.d. 7 days) or topical agents (nystatin 1ml q.d.s 7 days).

Answer 93

Dexamethasone (4mg o.d) may help but the effect often wears off after 2-3 weeks. Megestrol acetate (160mg o.d) is effective for longer but may cause fluid retention.

Answer 94

Gastric stasis/irritation ‘Toxic’ causes Cerebral causes - Raised intracranial pressure , Anxiety, anticipatory nausea and vomiting Vestibular causes Constipation Intestinal obstruction

Answer 95

Features Early satiety, epigastric fullness, hiccups, heartburn, often minimal nausea between vomits. May be caused by tumour, hepatomegaly, ascites (‘squashed stomach’) and dysmotility (drugs, autonomic failure). Treatment Metoclopramide 10-20 mg po/sc 30 minutes before meals or 30-60 mg SC over 24 hours. Stop any causative drugs if possible. Consider proton pump inhibitor if gastric irritation.

Answer 96

Features Persistent or intermittent nausea, small vomits, ‘possets’, and retching. May be caused by drugs (opioids, digoxin, antiepileptics), hypercalcaemia, uraemia and infections (UTI, pneumonia) . Treatment Haloperidol 1.5-5 mg po/sc nocte.

Answer 97

Features Early morning headache, vomiting, may be little nausea. Associated neurological symptoms/signs. Treatment Dexamethasone 8-16 mg po od (reduced if possible) plus Cyclizine 50mg TDS po/sc or 150mg SC/24hours.

Answer 98

Features May have specific precipitants such as certain situations, overly anxious or depressed Treatment Benzodiazepines, cognitive behavioral therapy, complementary therapies Indeterminate Consider levomepromazine 6.25-12.5mg nocte po/sc.

Answer 99

Features - May be associated with movement, hearing loss, vertigo or tinnitus Treatment Consider cyclizine, hyoscine or cinnarizine

Answer 100

Constipation is very common in palliative care patients due to a combination of factors including immobility, reduced food and fluid intake, drugs (e.g. opioids), bowel pathology and hypercalcaemia.

Answer 101

Laxatives can be classified as predominantly • bulk forming - e.g. fybogel are rarely appropriate in palliative care patients. * stool softeners - e.g. lactulose and sodium docusate. Lactulose may cause significant bloating and flatulence. Movicol is predominantly a softener but may also stimulate bowel motions; each sachet requires 125mls of liquid to be swallowed. * stimulants - e.g. senna and dantron. Avoid stimulants if the patient has colic. Some laxatives contain both a softener and a stimulant (e.g. co-danthrusate = dantron + docusate). Most patients require a softener and a stimulant.

Answer 102

For opioid induced constipation co-danthrusate, co-danthramer or movicol are the drugs of choice. Review laxatives every 2 days. If bowels haven’t moved in 3 days, consider rectal examination and the use of suppositories and enemas.

Answer 103

Intestinal obstruction in advanced cancer is frequently incomplete, intermittent, and at multiple sites. There is a high incidence in patients with ovarian and bowel cancer.

Answer 104

``` Symptoms vary depending on the level and degree of obstruction and may include any or all of the following: • Nausea and vomiting • Colicky pain • Abdominal distension • Dull aching pain • Diarrhoea and/or constipation ```

Answer 105

Surgical intervention will depend on the patient’s disease status and co-morbidity, level of the obstruction, and co-existing symptoms. Intravenous fluids and nasogastric tubes may be appropriate as a short-term intervention but are rarely appropriate for long-term management. Oral intake of food and drink can continue for the patients’ enjoyment and is often surprisingly well tolerated. The patient will decide if the risk of vomiting outweighs the pleasure of eating. Medication should generally be given by continuous subcutaneous infusion. A combination of antiemetics, analgesics, antispasmodics is usually required. If colic is a feature, stimulant laxatives and prokinetic drugs (metoclopramide) should be stopped and antispasmodics prescribed (hyoscine butylbromide). Dexamethasone and octreotide may also be used.

Answer 106

Asthma - Bronchodilators Pulmonary oedema - Diuretics, diamorphine Pulmonary embolism - Anticoagulants e.g. tinzaparin

Answer 107

Exacerbation of COPD - Antibiotics, bronchodilators Pneumonia - Antibiotics, physiotherapy Bronchial obstruction by tumour - Dexamethasone, stents or laser Superior vena caval obstruction - Dexamethasone, urgent stenting

Answer 108

Congestive cardiac failure - Diuretics, digoxin, ACE inhibitors Anaemia - Transfusion may help Pleural effusion - Pleural aspiration / pleurodesis Ascites - Paracentesis if appropriate. Lymphangitis carcinomatosis - Trial dexamethasone

Answer 109

Dyspnoea is frightening to the patient, family and staff. Discussion of fears and explanation are vital. Modification of lifestyle, breathing retraining and relaxation may be beneficial. Oxygen may help acute dyspnoea but many patients requiring palliation for breathlessness will not benefit from oxygen therapy. A fan directed onto the face often helps dyspnoea.

Answer 110

Oral opioids decrease respiratory effort and therefore breathlessness. Improvements are seen at doses that do not cause respiratory depression Oral morphine (e.g. oramorph 2.5mg four hourly) if opioid naïve. Gradually titrate dose upwards according to response. In patients already taking oral morphine try the usual breakthrough dose.

Answer 111

Lorazepam (0.5mg-1mg sub-lingual) may help anxiety associated with breathlessness or give relief during panic attacks. Midazolam (2.5mg-5mg subcut) may benefit patients who can’t tolerate oral/sub-lingual route.

Answer 112

Cough may be caused by excessive production of fluid in the lung (e.g. excessive mucus production by tumour, bleeding from a tumour), inhaled foreign bodies, or abnormal stimulation of the airways receptors. Treat the underlying cause if possible.

Answer 113

If the cause cannot be reversed symptomatic treatment should be started. If the patient is having difficulty expectorating, a trial of saline nebulisers may be helpful. If the cough is dry and irritating then simple linctus may help, alternatively opioids are cough suppressants (e.g. codeine linctus, normal release oral morphine). Remember to prescribe laxatives with opioids.

Answer 114

breast, bronchus and prostate but MSCC can occur with any tumour

Answer 115

Two thirds occur in the thoracic region and the remainder in the cervical or lumbar spine

Answer 116

* Back pain or nerve root pain, either unilateral or bilateral, which may be aggravated by movement, coughing or lying flat. Pain may precede other symptoms or may be absent in some patients. * Motor weakness may be rapid or slow in onset and can be subtle in the early stages. Descriptions of perceived changes in strength are important. * Subjective sensory disturbance often precedes objective physical signs e.g. ‘it feels like I am walking on cotton wool’. * Bladder/bowel dysfunction generally occurs late. Urinary retention often develops insidiously.

Answer 117

* Weakness/paraparesis/paraplegia. * Changes in sensation occur below the level of compression. They may be asymmetrical and may not necessarily be complete. * Reflexes are usually increased below the level of the lesion. * Clonus and painless bladder distension may be present.

Answer 118

Whole spine MRI is the investigation of choice. Plain X-rays are not helpful in diagnosing MSCC.

Answer 119

Dexamethasone 16mg - any clinical suspicion of cord compression Subsequent treatment may involve surgery, radiotherapy or chemotherapy, either alone or in combination. Surgery is usually favoured in situations of mechanical collapse of a vertebral body (where radiotherapy will rarely reverse the situation) but is less likely to be used if there is extensive disease elsewhere. Management is time critical. Outcomes correlate with the level of function at the time of treatment. Complete paralysis, that has been present for several days, is almost never reversible.

Answer 120

extrinsic compression, thrombosis, or invasion of the wall of the superior vena cava. It is most commonly caused by extensive lymphadenopathy in the upper mediastinum (often in patients with lung cancer or lymphoma) but can occur with any solid tumour

Answer 121

* Headache or a “feeling of fullness” in the head * Facial swelling * Dyspnoea (often worse on lying flat) * Cough * Hoarse voice

Answer 122

* Facial / upper limb oedema * Prominent blood vessels on the neck, trunk and arms * Cyanosis

Answer 123

dexamethasone 16mg daily - produce short-term relief of symptoms. Urgent vascular stenting is the usual treatment of choice - often followed by radiotherapy or chemotherapy depending on the primary tumour type. If this is the initial presentation of a cancer then a biopsy will be important. Many of the common tumour types presenting in this way can progress very rapidly (eg small cell lung cancer, lymphoma, germ cell tumours) and this may well need arranging urgently to guide management. If a germ cell tumour is possible then tumour markers (AFP, βhCG, LDH) may be useful.

Answer 124

Hypercalcaemia can be associated with most tumours, but is commonly seen in patients with breast cancer, lung cancer, squamous cell carcinomas and myeloma. A patient may develop hypercalcaemia without having bone metastases.

Answer 125

``` Early symptoms include: • lethargy • malaise • anorexia • polyuria • thirst • nausea • vomiting • constipation ``` ``` Late features include • confusion • drowsiness • fits • coma ```

Answer 126

Serum calcium corrected for serum albumin.

Answer 127

Aggresive Rehydration using normal saline followed by intravenous bisphosphonate such as pamidronate or zoledronic acid. About 70% of patients respond. Maximum response is seen after 6-11 days, with an average duration of response of 3-4 weeks.

Answer 128

Symptom control must be fast and effective. Keeping green towels close by to absorb and reduce the visual impact of blood loss is beneficial. If time allows, intramuscular (into the deltoid muscle) or subcutaneous midazolam, as a sedative and amnesic can be given. It is important for a member of staff to stay with the patient once bleeding has started.

Answer 129

* Profound weakness * Confined to bed for most of the day * Drowsy for extended periods * Disorientated * Severely limited attention span * Losing interest in food and drink * Too weak to swallow medication

Answer 130

* Less vomiting and incontinence. * Reduction in barriers between patient and family/carers. * Prevention of painful venepuncture.

Answer 131

``` STOP: • Vitamins/iron • Hormones • Anticoagulants • Corticosteroids • Antibiotics • Antidepressants • Cardiovascular drugs • Anticonvulsants used for pain ``` START: Patients should generally be prescribed an analgesic, antiemetic, anti-secretory and anxiolytic that can be given subcutaneously if needed.

Answer 132

pain, urinary retention, faecal impaction, respiratory secretions. If no reversible cause can be found then sedation is often required. Midazolam is a useful short acting sedative/anxiolytic/muscle relaxant/anticonvulsant. It can be given subcutaneously either by stat doses (2.5mg-5mg sc) or infusion (starting at 10mg in 24hours). Sometimes levomepromazine may be needed.

Answer 133

This is a rattling noise produced by the movement of secretions in the upper airways, generally in patients who are too weak to expectorate effectively. Patients are generally not distressed by the noise but relatives and carers may find this distressing. Repositioning of the patient may help. Otherwise antisecretory drugs such as hyoscine butylbromide (Buscopan®) or hyoscine hydrobromide (which may cause paradoxical agitation) may be needed.

Answer 134

* have had previous multiple losses or recent losses * have ambivalent relationships * have dependent children * have lost a child * have previous psychological problems or substance abuse * live alone or feel unsupported

Answer 135

• Inability to swallow drugs due to reduced conscious level, often in the last few days of life • Persistent nausea and vomiting • Intestinal obstruction • Malabsorption of drugs • Dysphagia Inadequate pain control is not an indication for syringe driver use unless there is reason to believe oral analgesics are not being absorbed.

Answer 136

Diamorphine or morphine sulphate Analgesic 5mg - ? Upper limit determined by response and adverse effects Cyclizine Antiemetic 100-150mg May cause skin irritation Haloperidol Antiemetic/Antipsychotic 3-10mg Metoclopramide Antiemetic 30-60mg Useful prokinetic, Avoid if colic Levomepromazine Antiemetic/Antipsychotic/ Sedative 6.25-100mg Useful second line sedative at higher doses Can cause skin irritation Hyoscine butylbromide Antisecretory/ Antispasmodic 60-120mg Does not cross the blood brain barrier Hyoscine hydrobromide Antisecretory/ Antispasmodic 400mcg – 2.4mg May cause sedation or agitation Midazolam Sedative/Anxiolytic/Anticonvulsant 10-60mg

Answer 137

Carcinoma of the breast is the most common cancer in women, accounting for 15% of all new cases of female cancer. In the UK, 55000 new cases are diagnosed each year and approximately 11000 women die from the disease. It is estimated that in the UK 1 in 8 women and 1 in 870 men will develop breast cancer. It is a rare cancer in men.

Answer 138

* increasing age, * increased periods of oestrogen exposure (e.g. late childbearing, nulliparity, early menarche, late menopause, obesity) * Oral contraceptive pill and some types of hormone replacement therapy * Obesity * Alcohol * Ionising radiation * Family history (first degree relative, particularly premenopausal) * Genetics- Inherited mutations of certain genes confer a familial predisposition to breast cancer. Mutations of the BRCA 1 gene are associated with an increased susceptibility to breast and ovarian cancer. Mutations of BRCA 2 gene have been linked to early onset breast cancer and male breast cancer (but not with ovarian cancer).

Answer 139

Infiltrating or invasive ductal carcinoma is the most common cell type, comprising 70-80% of all cases. Lobular carcinoma, comprising approximately 10% of cases, is characterized by a higher incidence of multicentric tumours within the same or opposite breast. Other less common histological types include medullary, colloid, comedo and papillary. Tumours are graded according to differentiation with grade 1 lesions being well differentiated and grade 3 lesions being poorly differentiated.

Answer 140

Most patients present with a breast mass. Less common presentations would include nipple discharge, regional lymphadenopathy (axillary or supraclavicular nodes), or symptoms of metastatic disease.

Answer 141

• Clinical assessment - full history and examination • Bilateral mammography (to detect multicentric tumours or synchronous primaries in the opposite breast) • Targeted ultrasound (+biopsy) of the symptomatic breast area or area of mammographic abnormality. Patients will also have an ultrasound of the axillae +/- biopsy of suspicious nodes Cytological diagnosis should be confirmed by fine needle aspiration cytology (FNAC), needle biopsy, incisional or excisional biopsy.

Answer 142

In patients at high risk of disseminated disease, consideration should be given to performing isotopic bone scan and liver imaging with ultrasound or CT scan. MRI is performed if there is a discrepancy between clinical examination, mammogram and ultrasound findings, if breast density preludes accurate mammogram assessment and if the histology is lobular (as there is a higher frequency of multicentric disease)

Answer 143

``` T0 No primary tumour Tis In situ disease, non invasive T1 Invasive tumour less than 2 cm T2 Tumour between 2 and 5 cm T3 Primary tumour greater than 5 cm T4 Skin involvement ``` ``` N0 No lymph nodes N1 Mobile axillary nodes N2 Fixed axillary nodes N3 Internal mammary nodes ``` M0 No metastases M1 Distant metastases

Answer 144

``` Stage 0: Tis, N0, M0 Stage I: T1, N0, M0 Stage II: T2/3, N0, M0 or T0/1/2, N1, M0 Stage III: T or N > stage II, M0 Stage IV: Any T, Any N, M1 ```

Answer 145

The standard treatment would be surgery first. However for a certain subset of patients neoadjuvant chemotherapy is considered (chemotherapy before surgery) such as when • Initial surgery is not possible due to the size of the tumour • To allow for breast conservation • Her2 positive or triple negative breast cancer (ER, PR and Her 2 negative) as high response rates are possible

Answer 146

Surgical options include mastectomy or conservative surgery (e.g. wide local excision) with postoperative radiotherapy. Survival is equivalent with any of these options in appropriately selected patients. Selection of the appropriate therapeutic approach depends on • location • size of the lesion and breast size, • single or multifocal disease • the extent of in-situ change • patient’s preference. An assessment of axillary lymph node disease should be performed in all patients. This is normally performed at the same time as breast surgery. If the initial assessment shows evidence of metastatic involvement of the lymph nodes then patients will have an axillary clearance. If there is no evidence of metastatic involvement of the lymph nodes, patients will have a sentinel node biopsy (SNB).

Answer 147

The sentinel nodes are the first few lymph nodes into which a tumour drains. Sentinel node biopsy involves injecting a tracer material that helps the surgeon locate the sentinel nodes during surgery. The sentinel nodes are removed and analyzed in a laboratory. If they are positive then patients will go on to have an axillary clearance or radiotherapy to the axillae.

Answer 148

Systemic therapy with endocrine treatment or with cytotoxic chemotherapy is of proven value for the treatment of micro metastatic disease in the adjuvant setting. The following factors may be considered in selecting treatment: • Hormone receptor status [oestrogen receptor (ER) status] • HER-2 receptor status • Menopausal status • Tumour size and grade • Nodal involvement • Performance status

Answer 149

Combination chemotherapy significantly reduces the annual risk of recurrence (by 28%) and mortality (by 16%) when used in the adjuvant setting for breast cancer. The effect is greater in women less than 50 years of age. Whether adjuvant chemotherapy is advised is based on assessment of risk. Tools such as Adjuvant online and the Oncotype DX test can aid in decision making.

Answer 150

effective in metastatic and localized disease where the cancer over-expresses the target epithelial growth factor receptor (HER-2). In the adjuvant setting it is given for 12 months. It can affect cardiac function and therefore patients will need to have regular cardiac monitoring (normally with a MUGA scan).

Answer 151

normally prescribed for premenopausal women who have tumours that are ER/PR positive if there are no contraindications. Tamoxifen therapy, 20 mg/day, significantly reduces the annual risk of recurrence (by approximately 25%) and of death (17%) in the adjuvant setting. Increased thrombotic complications are reported and an increased risk of endometrial carcinoma. Tamoxifen is normally given for 5 years. However there is now evidence that for those patients at high risk of recurrence there is benefit for extending endocrine treatment to 10 years.

Answer 152

Aromatase Inhibitors. e.g. anastrazole, letrozole are demonstrated to have superior efficacy to tamoxifen in post-menopausal women with breast cancer. They have a different side effect profile including fewer vascular and malignant events, but more problems with osteoporosis. Patients will normally have a baseline DEXA scan to assess bone mineral density and further recommendations depending on the results (such as lifestyle changes, Vit D and calcium supplementation or bisphosphonates).

Answer 153

Following conservative surgery, all patients require radiotherapy to the residual breast tissue to reduce the chances of locoregional cancer recurrence. Local chest wall radiotherapy may also be indicated following mastectomy in those who are assessed as having a high risk of local recurrence (e.g. deep resection margin involvement, large primary tumours (> 4cm), multiple axillary lymph nodes containing metastatic disease, and widespread lymphovascular tumour permeation). In some situations the axillae or supraclavicular fossa are also irradiated. Standard treatment is daily, Monday to Friday, for three weeks. For young patients (under 50 years) or those with close surgical margins they will receive an additional week of radiotherapy to the tumour bed (referred to as a “boost”).

Answer 154

the extent of disease, hormone and HER2 receptor status and the patient’s symptoms, preferences and performance status. If the patient presents with metastases or is placed in stage 4 after assessment, surgery is not part of the treatment unless to palliate some particular site of disease.

Answer 155

Endocrine treatment can be used in ER/PR positive disease as primary treatment in slowly progressive disease, especially where there is no visceral involvement and the patient has minimal symptoms. One third of unselected patients with metastatic disease respond to endocrine therapies. The median duration of response to a single endocrine therapy is 1-2 years. A higher response rate to endocrine therapy can also be related to several other factors:¬ • The dominant site of disease (highest in women with disease in soft tissue, less in those with bone metastases and less again in those with visceral metastases). This may simply reflect ER status • An objective response to prior endocrine treatment. • Greater duration of previous disease free interval.

Answer 156

Anti-oestrogens (e.g. Tamoxifen at a dose of 20mg/day) or aromatase inhibitors (e.g. anastrazole, letrozole). They should be continued until documented evidence of disease recurrence Ovarian ablation: In premenopausal women, endogenous ovarian oestrogen production may be stopped by ovarian ablation (surgically or radiotherapy induced) or by the use of luteinizing hormone releasing hormone (LHRH) agonists.

Answer 157

palliate symptoms and to improve quality / duration of life. Choice of agents will depend on histology, hormone and HER2 status, patient’s performance status and any previous lines of chemotherapy they may have received.

Answer 158

major role in the palliation of locally recurrent disease and controlling symptoms such as pain due to bony metastasis.

Answer 159

``` Stage 5 year survival Stage I 95% Stage II 80 % Stage III 60 % Stage IV 25 % ``` Prognosis is also dependent on histological grade, nuclear grade, HER-2 and oestrogen receptor status

Answer 160

* Lung cancer is the 3rd most common cancer in the UK. * 1 in every 13 men and 1 in every 7 women are diagnosed with lung cancer in their lifetime * Lung cancer accounts for 22% of cancer related deaths in the UK * Only 10% of patients who are diagnosed with lung cancer live for 5 years or more.

Answer 161

* Genetic predisposition * Cigarette smoking * Increasing age * History of COPD * Industrial exposure to asbestos, chromium, arsenic and iron oxide * Exposure to radiation

Answer 162

Small cell lung cancer (accounts for ~15% of lung cancers) Non-small cell lung cancer (accounts for ~85% of lung cancers) - Squamous cell carcinoma (42% of NSCLC), Adenocarcinoma (39% of NSCLC), Large cell carcinoma (8% of NSCLC)

Answer 163

These are highly aggressive tumours which grow rapidly. They have usually metastasised and become inoperable prior to diagnosis. They can be very responsive to chemotherapy initially, but often relapse quickly. Overall, prognosis is generally poor. They can also be associated with paraneoplastic syndromes - most commonly causing SIADH, Cushing’s syndrome or Lambert Eaton Myesthaenic syndrome (LEMS).

Answer 164

These are often found centrally, close to the bronchi, and can present with bronchial obstruction. They are closely linked to cigarette smoking. Squamous cell cancers can also secrete PTH relate peptide (PTHrp) which can lead to malignancy-related hypercalcaemia.

Answer 165

Adenocarcinoma (39% of NSCLC) These tumours are often peripheral. They are more frequent in women, non-smokers and patients with previous asbestos exposure. In addition, adenocarcinomas are more commonly associated with activating mutations in EGFR and ALK (see below).

Answer 166

These are less differentiated than other NSCLCs and tend to metastasise early. Other types of lung cancers include carcinoid, mesothelioma, sarcoma and lymphoma.

Answer 167

non-specific symptoms of the primary tumour such as cough, dyspnoea, haemoptysis, chest pain, or recurrent chest infections. As most of these symptoms are common in smokers, late presentation is frequent. Occasionally, tumours are identified incidentally on x-rays or scans performed for some other reason. Tumours at specific sites may produce particular syndromes. For instance, apical tumours may invade the brachial plexus or sympathetic chain producing Horner's syndrome or pain in the distribution of the nerve routes involved (Pancoast's syndrome). Recurrent laryngeal nerve palsy and superior vena cava obstruction may be associated with mediastinal disease. Specific histologies may be associated with a particular pattern of presentation. For instance, clubbing is more frequent with squamous cell carcinoma. Sputum production may be excessive in bronchio-alveolar carcinoma. A wide variety of paraneoplastic syndromes may also occur with lung cancer.

Answer 168

CXR- More than 95 % of lung tumours are visible on a plain CXR at presentation. CT chest and upper abdomen- this is used to assess the extent of local and distant disease, principally in the lungs, mediastinum, pleura, liver and adrenal glands. CT/MRI scan of the brain may also be useful if brain metastases are suspected. PET scan- this is used in patients who are thought to have operable disease to check for distant metastases which may not be picked up on CT. Bronchoscopy - Fibre-optic or rigid bronchoscopy allows visualisation of the bronchial tree, tumour biopsy and bronchial washings to be taken. Endo-bronchial Ultrasound (EBUS) can be used to biopsy lymph nodes within the mediastinum. Other biopsy techniques- Trans-thoracic biopsy under radiological guidance is sometimes required for the biopsy of peripheral lung tumours, or distant metastatic disease e.g. liver metastases. Tumour markers - Neuron specific enolase (NSE) and lactate dehydrogenase (LDH) may provide useful indications of tumour activity. These are not routinely used. Pulmonary Function Tests – PFTs are important for assessing underlying lung disease / function. This may be important when deciding fitness for treatment. Cardiopulmonary exercise testing – This is important for patients who are being considered for surgical resection to ensure they are fit enough to undergo an operation.

Answer 169

use a simple system to stage small cell lung cancer - Limited disease - cancer is contained in a single area that can be treated with radiotherapy. i.e. is only in one lung and may be in nearby lymph nodes – for example, in the centre of the chest or above the collar bone Extensive disease - spread beyond a single area that can be treated with radiotherapy. TNM staging can also be used

Answer 170

TX - can’t be assessed. T0 - no sign of cancer. Tis -area of cancer cells contained within the inner lining of the lungs. T1 - cancer is contained within the lung. T1a < 1cm T1b 1cm - 2cm . T1c 2 - 3 cm T2 - 3cm - 5cm across.Or the cancer has one or more of the following features: it involves the main airway (the main bronchus) but is not close to the area where the bronchus divides to go into each lung it involves the inner lining of the chest cavity (the visceral pleura) part or all of the lung has collapsed or is blocked due to inflammation T2a between 3cm and 4cm. T2b 4cm and 5cm. T3 - 5cm to 7cm. Or there is more than one tumour in the same lobe of the lung. Or the cancer has grown into one or more of these structures: the chest wall (the structures around the lungs, such as ribs, muscles, cartilage, or the diaphragm) the nerve close to the lung (phrenic nerve) the outer covering of the heart (the pericardium) T4 > 7cm. Or it is in more than one lobe of the lung. Or it has spread into one or more of the following structures: the muscle under the lungs (the diaphragm) the area between the lungs in the middle of the chest (the mediastinum) the heart a major blood vessel the wind pipe (trachea) the nerve that controls the voice box the food pipe (oesophagus) a spinal bone the area where the main airway divides to go to each lung

Answer 171

NX means that the lymph nodes can’t be assessed. N0 means that the lymph nodes don’t contain cancer cells. N1 means there are cancer cells in lymph nodes within the lung or in lymph nodes in the area where the lungs join the airway (the hilum). N2 means there is cancer in lymph nodes:in the centre of the chest (mediastinum) on the same side as the affected lung or just under where the windpipe branches off to each lung N3 means there is cancer in lymph nodes: on the opposite side of the chest from the affected lung or above the collar bone or at the top of the lung

Answer 172

M0 means the cancer hasn’t spread to another lobe of the lung or any other part of the body M1 means the cancer has spread to other areas of the body. M1a means one or more of the following: there is cancer in both lungs there are areas of cancer around the heart or in the lining around the lung there is fluid around the lung or heart that contains cancer cells – this is called a malignant pleural effusion or a pericardial effusion M1b means that there is a single area of cancer outside the chest in an organ (such as the liver or brain) or a lymph node. M1c means that there is more than one area of cancer in one or several organs.

Answer 173

generally considered a systemic disease at presentation. As such, the vast majority of patients will receive palliative chemotherapy. If the disease appears “limited stage” at diagnosis (i.e. encompassable within a high dose radiotherapy field) then radical radiotherapy may be given (either alongside or following) the chemotherapy. If the disease is more extensive at presentation, then chemotherapy is the mainstay of treatment although consolidation thoracic radiotherapy may also be used in patients who have a good response to chemotherapy. Prophylactic cranial irradiation (see below) is also used in patients with limited disease and in those with extensive disease who respond to chemotherapy.

Answer 174

SCLC is one of the most chemo-sensitive solid tumours. Chemotherapy is therefore the mainstay of SCLC management with responses occurring within days. Approximately eighty per cent of patients with SCLC will respond to combination chemotherapy (with complete response rates approaching 50%). Most patients will sadly relapse, the majority within 12 months of chemotherapy, with disease that is chemo-resistant and will die from rapidly progressive disease.

Answer 175

1. Treatment of the primary tumour. Thoracic radiotherapy as consolidation after chemotherapy or as concurrent treatment improves overall survival in patients with limited disease. Local control is achieved with radiation, such that relapse usually occurs at a site distant to that of the primary disease. This pattern of relapse may result in improved palliative symptom control, i.e. patients are less likely to develop problems as a result of their primary tumour (such as bronchial obstruction or SVCO) 2. Prophylactic cranial irradiation (PCI). Brain metastases are frequent in SCLC and cause significant morbidity and mortality. PCI is offered to patients following a good response to chemotherapy and aims to prevent the development of brain metastases. It is also associated with improved survival, but is can have significant toxicities such as memory impairment, functional deficit and dementia. 3. Palliative. Radiotherapy may be used to palliate the symptoms of advanced SCLC, unresponsive to other treatments.

Answer 176

The early dissemination of SCLC means it should be considered a systemic disease at presentation. Surgical intervention is therefore inappropriate for the majority of cases. In patients who do undergo surgical resection, this is often when a single lesion is resected and unexpectedly turns out to be an early SCLC. There is no evidence of improved outcome as a result of the surgery and patients will usually require adjuvant chemotherapy and radiotherapy.

Answer 177

Prognostic factors include extent of disease at presentation, number of metastatic sites, performance status, degree of weight loss and biochemical abnormalities (elevated LDH or low sodium or albumin). Patients with limited disease, a good performance status, and favourable biochemistry have a small but real chance of long-term survival (10-15 %). Patients with extensive disease who are less fit are rarely cured but can obtain good palliation from chemotherapy.

Answer 178

Without treatment, SCLC has an extremely poor prognosis with a median survival of 2-4 months. For patients treated with systemic chemotherapy, the median survival is substantially improved: usually between 6-12 months.

Answer 179

Most patients with NSCLC die within 12 months of diagnosis. However, the prognosis is better in selected groups and active anti-cancer treatment may be appropriate.

Answer 180

Mediastinal involvement is considered a contraindication to surgery by most surgeons. Approximately 30% of people with NSCLC are suitable for surgery. Stage I and 2 (T1-2, N0-1) NSCLC, managed with surgical resection has a good prognosis (~80% 5-year survival) and the possibility of cure

Answer 181

There is a 3-5% mortality from a pneumonectomy. Therefore, more limited resections such as lobectomy or wedge resections are performed where possible / appropriate.

Answer 182

Following surgery, adjuvant chemotherapy may improve survival for patients fit enough to tolerate it. This is usually used for patients with nodal disease and larger tumours. Adjuvant radiotherapy may be used where there are positive surgical margins.

Answer 183

In patients with early stage disease, who are not suitable for surgery, radical radiotherapy has often been used and produces 20% 5-year survival for patients with stage 1 or 2 disease.

Answer 184

Continuous, hyperfractionated accelerated radiotherapy (CHART) is radiotherapy which is given three times a day for 12 consecutive days, and compared with conventional radiotherapy (often 20 to 30 once daily treatments), results in improved survival.

Answer 185

Giving radiotherapy at the same time as chemotherapy (concurrent chemo-radiotherapy) may also improve outcomes compared to giving chemotherapy first followed by radiotherapy (sequential chemo-radiotherapy). This is usually used in patients with Stage II-III disease.

Answer 186

early NSCLC located more peripherally in the lungs is treated by stereotactic ablative body radiotherapy (SABR). This delivers a small number (≤5) of very large doses of radiotherapy to a small, highly conformal volume around the lung tumour. This technique has rates of tumour control that are comparable to surgery and can be used in many patients who would not be fit enough for surgery.

Answer 187

Palliative radiotherapy is used frequently for symptomatic disease such as spinal cord compression, painful bone metastases or significant chest symptoms due to central disease (e.g. haemoptysis, cough).

Answer 188

Chemotherapy is the mainstay of treatment for patients with metastatic or locally advanced disease. The preferred choice of chemotherapy agents is dependent on the histological subtype of NSCLC.

Answer 189

Where there is no activating mutation/translocation or high PDL1 expression (see immunotherapy) combination regimens are used, either Carboplatin and Gemcitabine or Carboplatin/Cisplatin and Pemetrexed. Docetaxel can be used as a 2nd line option.

Answer 190

Patients with adenocarcinoma are tested for mutations in EGFR and ALK at the time of diagnosis. If these are positive, tyrosine kinase inhibitors (TKIs) can be used (e.g Afatinib/Erlotinib/Gefitinib for EGFR mutations and Crizotinib for ALK mutations)

Answer 191

shown in clinical trials to be beneficial in some patients with advanced non-small cell lung cancer The proportion of patients suitable for these treatments is < 10% overall but is higher in some ethnic groups and non-smokers

Answer 192

Immunotherapy (Pembrolizumab): has recently been approved for patients with advanced NSCLC in patients with high PDL1 expression (a molecule involved in controlling the normal immune response). This can be used either before or after chemotherapy and a small percentage of patients can have a prolonged benefit with this.

Answer 193

The outcome for patients with a diagnosis of NSCLC has recently changed due to the development of new targeted treatments and immunotherapy. Without treatment, prognosis is likely to be short, and is usually measured between 3-6 months. Provided patients are fit enough to tolerate chemotherapy, this can extend average life expectancy by a number of months, possibly to just over a year. If patients are suitable for targeted treatment or immunotherapy, this can be substantially longer and prognosis may be around 2 years in some cases.

Answer 194

Prostate cancer is the commonest cancer in males, with more than 47000 new cases diagnosed in the UK in 2015. It is predominantly a disease of older men, with more than 50% occurring over the age of 75.

Answer 195

no clear etiological agents, although radiation exposure, diet and anabolic steroids have all been implicated. These may alter the level of the male hormone testosterone which controls the growth, and function of the prostate. Risk of prostate cancer rises with age and varies by ethnicity, being higher in men from African and Afro-Caribbean backgrounds. Risk increases with family history of prostate cancer and for men whose mother was diagnosed with breast cancer. Mutations of BRCA II and the pTEN genes are associated with an increased risk

Answer 196

Over 95% of tumours are adenocarcinomas, developing in glandular tissue in the posterior or peripheral parts of the prostate gland. Benign prostatic hyperplasia more commonly arises in the centre of the gland

Answer 197

Prostate cancer may be asymptomatic and diagnosed by rectal examination or a prostate specific antigen (PSA) tumour marker blood test. Patients may present with local lower urinary tract symptoms (LUTS) including poor stream, nocturia, dribbling and increased frequency. Impotence is common. 1 in 5 patients present with metastatic prostate cancer and may have bone complications such as anaemia, pain, pathological fracture, or spinal cord compression.

Answer 198

Typical rectal examination findings would include an enlarged, hard, craggy gland (or nodule). Ultimately there is obliteration of the median sulcus.

Answer 199

Initial investigation includes digital rectal exam and serum prostate-specific antigen (PSA) blood test. Further investigation is based on clinical features, patient wishes and fitness. Most patients will have (ultrasound guided) transrectal biopsy to confirm the diagnosis but where clinical suspicion is very high (e.g. PSA >100 with positive bone scan) this is not required. Even in apparently localised prostate cancer high serum PSA may indicate occult metastases and shift the balance away from radical treatment.

Answer 200

If radical (curative) treatment is appropriate then an MRI scan can visualize the prostate well and delineate any extra-capsular spread.

Answer 201

If clinical features raise concern about metastatic disease then an isotope radionucleotide bone scan is useful to detect bone involvement.

Answer 202

Functional imaging: radiolabelled technetium is taken up by osteoblasts at sites of bone remodelling e.g. sclerotic bone metastases in prostate cancer

Answer 203

The TNM staging system (Simplified version): TX: Primary tumour cannot be assessed T0: No evidence of primary tumour T1: Clinically unapparent tumour not palpable nor visible by imaging T2: Tumour confined within prostate T3: Tumour extends through the prostate capsule T3a: Extracapsular extension (unilateral or bilateral) T3b: Tumour invades seminal vesicle(s) T4: Tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall N0 No regional lymph node involvement. N1 Regional lymph node involvement ``` M0: No distant metastasis M1: Distant metastasis M1a: Non-regional lymph node(s) M1b: Bone(s) M1c: Other or multiple site(s) with or without bone disease ```

Answer 204

The Gleason system scores tumours (from 2 to 10) on the basis of histological patterns in the two most dominant areas of the tumour, (e.g. Gleason 4 + 3 means main area is 4 with the second area 3).

Answer 205

often relatively indolent and can occur in patients whose age or co-morbidities make them more likely to die from other medical problems rather than the cancer. PSA, histological grade and stage can be used to stratify patients with local prostate cancer into risk groups and to counsel patients on management options. Treatment of locally advanced and metastatic patients is broadly palliative but can lead to durable symptomatic benefit and many patients live with their disease for years. . The most appropriate options are influenced by the patient’s age, fitness, existing medical issues and preferences.

Answer 206

In patients with asymptomatic disease, confined to the prostate, observation rather than active treatment may be appropriate, particularly where other conditions limit the length of survival that is expected. Radical treatment is unlikely to benefit men with life expectancy of less than ten years, some of whom will not require on-going surveillance. The optimum management of patients with an elevated PSA but no clinical evidence of prostate cancer is unknown.

Answer 207

Patients with localised disease (T2 disease or less) can be treated by radical prostatectomy with curative intent and this can be performed by perineal or retroperineal routes. Robotic laparoscopic surgery leads to reduced operating times, less blood loss and shorter hospital stays but, though mortality is low, prostatectomy can lead to temporary or lasting impotence and incontinence. Palliative surgical techniques such as trans-urethral resections may be used to relieve prostatic symptoms or urinary obstruction in some men.

Answer 208

Radical radiotherapy may be used as an alternative to surgery in T1 and T2 tumours, where PSA is low, suggesting no occult metastases. It is also more appropriate for the control of more advanced local disease. Adjuvant radiotherapy may also be given following radical surgery if there is concern for residual disease. Definitive radiotherapy should be delayed until at least six weeks following trans-urethral resection to prevent stricture formation. Palliative radiotherapy is used to palliate the primary tumour and/or to treat metastatic complications e.g. recurrent haematuria due to bleeding from prostate bed, bone pain from metastatic disease.

Answer 209

Radiotherapy may be performed by external beam irradiation, by the interstitial implantation of radioisotopes (brachytherapy) or by a combination of these. Side effects can include dysuria, rectal bleeding, diarrhoea, impotence and incontinence.

Answer 210

Hormonal treatments are used for treating advanced disease or in conjunction with radiotherapy for the treatment of localised disease. Inhibition of the growth-stimulatory effect of endogenous androgens may effectively treat prostatic cancer with a response rate of approximately 80%. A variety of hormonal options are available

Answer 211

LHRH agonists (e.g. leuprorelin, goserelin) - LHRH interferes with the normal release of gonadotropins from the pituitary. This reduces the level of circulating testosterone to those following castration. LHRH agonists are given by monthly or 3 monthly subcutaneous or intra-muscular depot injections. Side effects include impotence, loss of libido and tumour flare. Tumour flare occurs on initiation of treatment (prior to the down regulation of gonadotropin) and is avoided by short-term concomitant anti-androgen therapy. Long-term consequences of medical castration include increased cardiac risk and osteoporosis. Gonadotrophin-releasing hormone antagonist (degarelix) leads to castrate levels of testosterone in 96% of patients within 3 days (without risk of tumour flare). Given by monthly subcutaneous injection it is indicated when tumour flare may lead to significant symptoms e.g. a patient presenting with metastatic spinal cord compression. Oestrogen therapy. Oestrogens inhibit LHRH production from the hypothalamus but are rarely the best option due to side effects: impotence, loss of libido, gynaecomastia, myocardial infarction, stroke and pulmonary emboli. Anti-androgens (e.g. bicalutamide, enzalutamide) compete with androgens for sites on the androgen receptor. Enzalutamide shows progression and survival benefit when combined with LHRH therapy in advanced prostate cancer. Bilateral orchidectomy is still widely used in countries without easy access to medical therapy.

Answer 212

Cytotoxic treatment with docetaxel (in combination with prednisolone) and cabazitaxel has been shown to improve quality of life and overall survival in patients with castrate-refractory metastatic disease six cycles of chemotherapy in fit men prolongs survival (median 60 months, ie an extra 15 months

Answer 213

Prostate cancer survival of men with low risk localised prostate cancer is excellent (99%) at 10 years whether they choose active surveillance, radiotherapy or surgery. Prostate cancer 10 year survival (all UK patients) is around 84%. Patients with metastatic disease have a median survival of 3.5 years. Pattern of disease (bone metastases), aggressive pathology and younger age are associated with a poorer prognosis.

Answer 214

Approximately 41,000 new cases are diagnosed each year in the UK. Colorectal carcinoma is the fourth most common malignancy after lung cancer, comprising 10-15% of all malignancies and causes 16,000 deaths each year. Cancer of the colon is 1.5 times more common than rectal carcinoma.

Answer 215

* Diet. A diet rich in animal fats and meat and poor in fibre, common in Western countries, has been suggested as a cause for some colorectal cancers. This may be reflected in the lower incidence in Africa, South America and Asia. * Inflammatory bowel disease. There is an association with ulcerative colitis (cumulative risk of 7 -15 % at 20 years of disease) which is related to the extent of the bowel involvement and the duration of the inflammation. An association with Crohn's disease is controversial. * Familial association. Several familial conditions are described, which account for 5-10% of colorectal tumours. These include hereditary non-polyposis colon cancer (HNPCC), familial adenomatous polyposis (FAP) and Gardner's syndrome. Specific gene defects associated with these conditions have been identified. For example, mutations in the APC gene (5q21-22) (familial adenomatous polyposis coli) and mutations in DNA mismatch repair genes (HNPCC).

Answer 216

* Epithelial: 90-95% adenocarcinoma (mucinous or signet ring). Rare others include squamous cell carcinoma and adenosquamous carcinoma. * Carcinoid * Gastrointestinal stromal tumour * Primary malignant lymphoma

Answer 217

Approximately 40% of large bowel cancers occur in the rectum, 20% in the sigmoid colon, 6% in the caecum and the rest in the remaining colon.

Answer 218

Colorectal cancer normally spreads by local invasion, lymphatic, venous and trans-coelomic spread within the peritoneal cavity.

Answer 219

Presentation can be with classical features of altered bowel habit, weight loss, rectal bleeding and vague abdominal pain, although the clinical features vary according to the site of the primary tumour and degree of spread. More occult tumours, typically of the right side of the colon and the caecum, can present with iron deficiency anaemia.

Answer 220

A rectal examination is essential- three quarters of all rectal lesions can be felt by digital examination. Direct visualisation of the bowel with rigid sigmoidoscopy (to 25 cm), flexible sigmoidoscopy and colonoscopy allows biopsy of suspicious lesions. Double contrast barium enema is less useful as no histology is provided. CT provides staging and a useful evaluation of the bowel in some cases. CT colonography combines CT scanning (for staging) with insufflation of the whole colon with gas. This can help identify synchronous polyps within the bowel where colonoscopy is not possible. However, it clearly does not facilitate biopsy. Other investigations include measurement of the tumour marker CEA (carcino-embryonic antigen). Although elevation of this protein is not diagnostic it can be useful to monitor disease.

Answer 221

A Invasion into but not through the bowel wall B Invasion through the bowel wall but not into nodes C Lymph node involvement D Distant metastases

Answer 222

TX: Primary tumour cannot be assessed T0: No evidence of primary tumour T1: Tumour invades submucosa T2: Tumour invades muscularis propria T3: Tumour extends through muscularis propria into peri-colic tissues T4: Tumour invades visceral peritoneum or invades / adheres to adjacent organ or structure N0 No regional lymph node involvement. N1 Involvement of 1-3 lymph nodes N2 Involvement of 4 or more lymph nodes MX: Distant metastasis cannot be assessed (not evaluated by any modality) M0: No distant metastasis M1: Distant metastasis M1a: Confined to one organ or site (e.g. liver or lung) but not peritoneum M1b: 2 or more sites (but not peritoneum) M1c: Peritoneal spread

Answer 223

Radical resection is the standard treatment for primary colorectal carcinoma because of the risk of unsuspected nodal metastases. Patients with early stage colorectal carcinoma are usually cured by surgical resection alone. The long-term results with rectal carcinoma are related to the initial surgical resection. Surgery may also be indicated in patients with advanced disease. Resection of liver metastases in addition to the primary may be beneficial. Further resection of a local recurrence is associated with improved long-term survival. Surgery or colonic stenting may be used in the palliative setting to manage or prevent an obstructing lesion.

Answer 224

Radiotherapy is predominantly used in the treatment of rectal carcinomas. It is not commonly used in the management of colon cancers because of the potential toxicity to adjacent organs and the mobility of the tumours. Pre-operative (or rarely adjuvant) radiotherapy is indicated in high risk rectal carcinomas before (or rarely following) total resection. Cases are selected on the basis of pelvic MRI staging scans. Local recurrences can be palliated with radiotherapy. Metastatic disease may also respond to palliative radiotherapy.

Answer 225

Adjuvant chemotherapy for high-risk colorectal carcinoma has become accepted practice. In a case of Dukes' C carcinoma, 6 months of adjuvant treatment may increase long term survival from 40% to 60%. Current trials do not indicate a clear role of adjuvant chemotherapy for Dukes' B carcinoma, although selected high risk cases are sometimes treated. Increasingly this is influenced by genetic testing of the tumour. 5-FU is the most active agent in colorectal carcinoma with a response rate of approximately 25%. Newer drugs such as Oxaliplatin and Irinotecan are now also in standard use.

Answer 226

``` 5 year survival Stage A 80% Stage B 50% Stage C 15-40% Stage D 5% Age below 40 is an adverse prognostic factor possibly reflecting a biologically more aggressive tumour. ```

Answer 227

Faecal occult blood testing of average-risk populations (with follow up colonoscopy for positive cases) has demonstrated a reduction of mortality between 15-18%.

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