Malignant Diseases eBook Flashcards

Question

Chemotherapy of Lung Cancer

Answer 1

SCLC should largely be treated with platinum-based combination chemotherapy for 4 – 6 cycles as first line. In NSCLC adjuvant chemotherapy can be indicated after surgery or if surgery is not an option in more advanced disease as palliative treatment. This usually consists of a cisplatin combination regime. Cisplatin at doses ≥50mg/m2 has a very high emetogenic potential which can lead to serious consequences for the patient. To minimise the risk of emesis, it is imperative that the patient receives the correct prophylactic anti-emetic therapy before and after treatment

Answer 2

Pembrolizumab is indicated for treatment of NSCLC in patient with specific mutations. It has been on the market for a few years; however it is now being used more within clinical practice.

Answer 3

Erlotinib and gefitinib are inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase. The overproduction of EGFR is common in NSCLC and is associated with aggressive tumours, resistance to chemotherapy and reduced survival. They are advantageous in that they don’t cause myelosuppression but they do have other side effects. In patients taking erlotinib 75% of them develop a rash and 54% diarrhoea. The range of targeted therapies is expanding to allow more options for treatment. These include Crizotinib and Ceritinib.

Answer 4

This is the third most common cancer in the UK after breast and lung cancer with a slightly higher incidence in males than females. It is one of the top four common cancer related deaths in the UK. Colorectal cancer is defined as cancer that develops in the colon or rectum. A high proportion appears to be caused by diet and lifestyle as it is more common in westernised countries than Asia or Africa.

Answer 5

 Age > 60 years  Diet – low dietary fibre, high animal fat, high sugar  Low physical activity  Smoking  Alcohol intake > 4 units daily  Inflammatory bowel disease (7 in 100 people with disease for 20 years)  Family history of bowel cancer (especially if diagnosed <45yrs)  Colorectal polyps  Obesity  Diabetes mellitus

Answer 6

``` Change in bowel habit Abdominal pain Rectal bleeding Blood in stool Anorexia or weight loss Anaemia Intestinal obstruction Palpable mass in rectum Tenesmus ```

Answer 7

The gold standard of diagnosis is colonoscopy which gives a visual appearance of the cancer, but also allows biopsy and a definitive histological diagnosis. Flexible sigmoidoscopy can be offered to patients with major comorbidity followed by a barium enema. A virtual colononography (CT scan) in the older age group with major comorbidity avoids the risks of colonoscopy, but does not give a tissue diagnosis of carcinoma. Once a diagnosis is made the stage of the disease is determined by CT scan of the chest, abdomen and pelvis, looking for depth of invasion and evidence of metastatic disease.

Answer 8

Surgery is the mainstay of colorectal cancer treatment and involves wide resection of the tumour. The two ends of the bowel are then either reconnected or a colostomy is formed. The type of surgery performed depends on where the cancer is located in the bowel. Radiotherapy is used for the treatment of rectal cancer in addition to surgery either as neoadjuvant therapy (to shrink the tumour and improve the chances of a complete excision) or adjuvant treatment.

Answer 9

Chemotherapy is commonly used as adjuvant treatment following surgery. 5-fluorouracil (5-FU) has traditionally been the treatment of choice for colorectal cancer and still plays a very important role in the treatment of colorectal cancer. Newer agents have been introduced in the last few years which have improved the treatment of colorectal cancer e.g. oxaliplatin, irinotecan & oral capecitabine. Adjuvant chemotherapy depends on the staging of the cancer.

Answer 10

This is usually treated with a combination of surgery and chemotherapy.

Answer 11

Cetuximab (Erbitux®) is a recombinant monoclonal antibody used in metastatic colorectal cancers expressing epidermal growth factor receptor (EGFR). It is given as combination therapy, or as monotherapy if oxaliplatin and irinotecan based treatment have failed or not been tolerated. It is administered by intravenous infusion and needs pre-treatment with an antihistamine and a corticosteroid before infusion to prevent hypersensitivity reactions. Survival has improved over the last 30 years due to better treatments, improved diagnostic and surgical techniques, specialist multidisciplinary teams and improved chemotherapy regimens. Other biological therapies used to treat metastatic colorectal cancers include bevacizumab and panitumumab.

Answer 12

Prostate cancer is the most common cancer in men in the UK. A quarter of all new cases of cancer diagnosed in men are prostate cancers, however mortality rates are relatively low and men usually die with it rather than from it. Prostate cancer is increasingly being treated primarily in the community so it’s important for pharmacists to have an understanding of the disease and the treatment.

Answer 13

No modifiable risk factors have been identified so there is no evidence on which to base a prevention strategy. Proven risk factors include:  Age is the biggest risk factor and prostate cancer is rare in men under 50 years.  Family history  Ethnicity Other possible risk factors include:  Diet  Obesity  Sexually transmitted infections In the UK, black Caribbean and African men (who have high androgen levels) have approximately a two to three times higher risk of being diagnosed or dying from prostate cancer than white men. Asian men generally have a lower risk than the national average (they also have lower androgen levels). Risk increases two to three times for men with a first-degree relative diagnosed with prostate cancer. Men who have relatives with breast cancer may also have a higher risk of prostate cancer and this is thought to be due to an inherited faulty gene.

Answer 14

The prostate gland lies at the base of the bladder surrounding the upper part of the urethra. The prostate makes stores and secretes an enzyme-rich fluid that makes up about 1/3 of the ejaculate volume. It liquefies semen and protects sperm during fertilization Symptoms do not usually present until the tissue surrounding the prostate gland is invaded. These may include:  Frequency & difficulty in urinating e.g. hesitancy, poor urinary stream and incomplete emptying.  Haematuria  Nocturia  Weight loss  Bone pain  Anaemia

Answer 15

- A digital rectal examination (DRE) is a key investigation in diagnosing prostate cancer and a high prostate specific antigen (PSA) (usually in primary care) is usually indicative. - Transrectal ultrasound guided biopsy may be indicated if cancer is suspected because of a raised PSA and the findings of the DRE. - Prostate cancer is staged using the Gleason score, PSA result and the TNM system. - The Gleason score is based on the microscopic appearance of biopsy tissue, ranging from 2 – 10. The higher score has a more abnormal appearance, are more aggressive cancers and have a worse prognosis.

Answer 16

The aim in prostate cancer is to prevent mortality and morbidity and keep side effects to a minimum. Treatment depends on the stage of disease and the risk stratification; most patients receive one or a combination of treatments as their disease progresses. Treatment efficacy in prostate cancer is complicated by side-effects that may profoundly affect a patient’s quality of life, such as erectile dysfunction and urinary incontinence. Both of these are common following radical treatment with surgery and radiotherapy. Options for the treatment of prostate cancer include: Watchful waiting or active surveillance (low risk prostate cancer) Surgery – prostatectomy (removal of prostate), Transurethral Resection of the Prostate (TURP) or orchidectomy (removal of testes) Radiotherapy – used in early stages for prostate cancer and in advanced metastatic cancer to treat painful bone metastases Hormone therapy Chemotherapy – an option in advanced hormone refractory disease

Answer 17

Androgen deprivation therapy (ADT) is used to reduce circulating testosterone levels which are the critical growth factor for prostate cancer. This is done by surgical or chemical castration. Chemically this is achieved with gonadorelin analogues, gonadorelin-releasing hormone antagonists (degarelix) and anti-androgens. Gonadorelin is secreted by the hypothalamus and acts at receptors on the pituitary gland causing it to secrete luteinising hormone and adrenocorticotropic hormone. These act on the testis (mainly) and adrenal gland respectively to increase testosterone. The gonadorelin analogues eg goserelin, leuprorelin bind irreversibly to receptors and prevent further activation and continuous administration inhibits luteinising hormone release. They are mainly available as depot intramuscular or subcutaneous injections. Anti-androgens (cyproterone, bicalutamide) block androgen receptors on the cell surface and therefore block the effects of testosterone or can reduce the production of testosterone. Other agents include abiraterone and enzalutamide. They are indicated for metastatic hormone-relapsed prostate cancer and the use of these agents have increased.

Answer 18

Patients with prostate cancer may respond to hormone therapy initially but resistance develops as disease progresses. These hormone refractory patients have a poor prognosis and the aim of treatment is to improve their symptoms, prolong life and slow progression of the disease. Chemotherapy is an option for these patients and docetaxel is now the gold standard. Other agents include cabazitaxel.

Answer 19

``` Currently the most common haematological malignancies are:  Leukaemia  Non-Hodgkin’s lymphoma  Hodgkin’s lymphoma  Myeloma ``` Haematological malignancies derive from a single cell in the bone marrow or the peripheral lymphoid tissue that has undergone genetic alteration. This cell then undergoes mitotic divisions to give rise to a clone of cells which proliferate excessively and may be resistant to apoptosis.

Answer 20

Haemopoiesis is the process of making blood cells and after birth this occurs in the bone marrow. The basic marrow stem cell differentiates into two types of stem cells, the lymphoid (which produces T and B lymphocytes and natural killer cells) and the myeloid (which produces erythrocytes, granulocytes, monocytes and megakaryocytes). Platelets (thrombocytes) are not true blood cells, but are cytoplasmic fragments of the megakaryocytes. T-cells are lymphoid cells that differentiate via action of the thymus gland. All the cell lines except erythrocytes (red blood cells) and megakaryocytes are involved with immune responses. Haemopoiesis is under the control of growth factors, inhibitors and the bone marrow. Erythropoetin produced by the kidney increases the number of red blood cell precursors, thrombopoietin produced mainly in the liver stimulates the formation of platelets and several cytokines stimulate proliferation of progenitor cells in the bone marrow. The rate of blood cell production is controlled by the body’s needs. Normal blood cells last for a limited time (ranging from a few hours to a few days for white blood cells, ~ 10 days for platelets and ~120 days for red blood cells) and must be replaced constantly

Answer 21

These include: • Radiation • Exposure to chemicals & cytotoxics • Viruses e.g. HIV, Epstein Barr • Genetic predisposition e.g. Down’s syndrome, trisomy 21, Fanconi’s anaemia • Predisposing haematological diseases e.g. myelodysplasia, aplastic anaemia, myeloproliferative diseases.

Answer 22

The leukaemias are a group of illnesses that are characterised by a proliferation of malignant white cells or their precursors in the bone marrow and blood. The types of leukaemia differ in their cellular origin and clinical behaviour and it is important to recognise this when looking at statistics on incidence and mortality of ‘leukaemia’ as a whole.

Answer 23

Acute Chronic Myeloid origin - Acute Myeloid Leukaemia AML Lymphoid origin- Acute Lymphoblastic Leukaemia ALL Chronic: Myeloid origin - Chronic Myeloid Leukaemia CML Lymphoid origin - Chronic Lymphocytic Leukaemia CLL

Answer 24

 Acute lymphoblastic  Acute myeloid (myeloblastic) Acute malignancies are those that appear and progress over a short timescale (days or weeks) and the tumour cells are usually morphologically immature (blasts). The malignant transformation occurs in the haemopoietic stem cell or early progenitors. Normal bone marrow is replaced by these malignant blast cells, there is a rapid increase in the number of immature blood cells and organ infiltration can occur. Acute leukaemias are usually aggressive diseases that need immediate treatment. They are easier to cure than chronic leukaemias.

Answer 25

These can include: • Anaemia –shortness of breath, tiredness, weakness, pallor • Leucopenia – recurrent infections, fever, malaise • Thrombocytopenia – bleeding & bruising • Organ infiltration – bone pain, lymphadenopathy, splenomegaly, hepatomegaly. Most of the signs and symptoms relate to anaemia, thrombocytopenia, and neutropenia which indicate a failure of normal haemopoiesis.

Answer 26

Many of the presenting symptoms of all haematological cancers are similar and their diagnosis is performed on blood tests, bone marrow biopsy & aspirate and lumbar puncture to determine if leukaemic cells are present in the cerebrospinal fluid. Histochemistry, immunophenotyping and cytogenetics are done on the bone marrow aspirate. These are all important in determining the most appropriate treatment for the patient. Findings may include:  Blood count – Haemoglobin low, white cell count usually raised (up to 200 x 109/L) but sometimes normal or low, platelets low  Blood film – blast cells seen  Bone marrow aspirate – hypercellular with infiltration by blast cells (>20% and up to 80-90% of marrow cells)  Chest X-ray – mediastinal widening can be present in T lymphoblastic leukaemia. Usually bone marrow is aspirated from the posterior iliac crest but alternative sites are the sternum & the medial part of the tibia (infants).

Answer 27

Chemotherapy is usually given in phases: 1. Remission induction therapy - The first phase of chemotherapy and steroids is to achieve remission with high dose intensive chemotherapy. The patient has a high tumour burden and is at risk of the complications of bone marrow failure and leukaemic infiltration. Intensive chemotherapy aims to rapidly reduce or eradicate leukaemic cells from the peripheral blood and bone marrow and to reestablish normal haemopoiesis. Remission is defined as < 5% blasts in the bone marrow, normal peripheral blood count and no symptoms or signs of leukaemia. 2. Intensification - The next phase is blocks of intensification (consolidation) using high dose multidrug chemotherapy to completely eradicate or reduce (to very low levels) the tumour burden. 3. Central nervous system directed therapy is required to prevent or treat central nervous system disease as generally the chemotherapy agents given systemically don’t reach the cerebrospinal fluid. 4. Maintenance therapy is usually given for 2 years with daily mercaptopurine and once weekly methotrexate. Intravenous vincristine and oral corticosteroids are given monthly in children or 3 monthly in adults as part of their maintenance treatment.

Answer 28

Chemotherapy for AML is in two phases:  Induction  Consolidation Course numbers and further treatment depend on the patients risk stratification according to their cytogenetic profile. “Good risk” patients usually have two courses of induction chemotherapy followed by one or two courses of consolidation chemotherapy. Cytarabine and an anthracycline such as daunorubicin are usually the backbone of AML chemotherapy. Intermediate or high risk patients can be considered for allogeneic stem cell transplant as chemotherapy by itself is associated with a significant risk of relapse. Prognosis in AML is very much governed by age at diagnosis with patients < 65 years having a higher 5 year survival rate than > 65 years.

Answer 29

Chronic leukaemias have a slower progression than acute leukaemias but they are more difficult to cure. The tumour cells can be difficult to distinguish morphologically from normal cells. They can be discovered on taking blood tests for other conditions by chance.

Answer 30

CML is a clonal myeloproliferative disorder characterised by increased neutrophils and their precursors in peripheral blood and increased cellularity of the marrow as a result of an excess of granulocyte precursors. Most patients with CML carry a chromosomal abnormality known as the Philadelphia chromosome (>90%). It most commonly occurs between the ages of 40 and 60 years but can occur at all ages. It is separated into three distinct phases:  Chronic phase – lasting on average 4 – 6 years  Accelerated phase – lasting approximately 6 – 12 months  Blastic phase (or blast crisis) – usually fatal within 6 months Patients usually present in the chronic phase with symptoms which may include weight loss, malaise and fatigue, unexpected bruising and bleeding, night sweats, itching, abdominal discomfort, hepatomegaly, bone tenderness, low haemoglobin and raised white cell count.

Answer 31

Fatigue, lethargy, pallor- Reduced/ineffective erythrocytes Headaches & confusion- Hyperviscosity of blood from increased white cell count (WCC) Weight loss & sweating (especially at night)- Raised metabolism from tumour load Splenomegaly- Spleen trying to ↓ WCC Gout or renal impairment- ↑ uric acid from destruction of WCC Bruising/bleeding- ↓ or ineffective platelets Bone pain- Bone marrow infiltration of WCC

Answer 32

There are several treatment options for CML available. Tyrosine kinase inhibitors – Standard dose Imatinib or nilotinib are now regarded as first line treatment of Philadelphia chromosome-positive CML in the chronic phase and have made a major improvement on the prognosis for patients with CML. Imatinib is also first line in accelerated phase or blast phase but only if it hasn’t been used previously. In patients who have taken imatinib in the chronic phase and have then advanced to the accelerated phase imatinib won’t be effective and nilotinib is indicated in these patients. Some resistance to imatinib has been identified and the newer tyrosine kinase inhibitors, dasatinib (not recommended first-line by NICE) and nilotinib, have a greater potency in imatinib-resistant patients. Interferon was previously considered the gold standard treatment for CML but is no longer recommended as first line treatment. It can be used for patients unable to tolerate tyrosine kinase inhibitors and post bone marrow transplant if disease recurs. Other treatments include hydroxycarbamide or busulphan which reduce the white cell count but have no effect on the long-term outcome of CML.

Answer 33

CLL involves mature-appearing, defective neoplastic lymphocytes with an abnormally long life span. The peripheral blood, bone marrow, spleen, and lymph nodes undergo leukaemic infiltration. It is the commonest leukaemia in the Western world and the peak incidence is between 60 and 80 years. Men are twice more likely to develop CLL than women. Most patients are symptomless and diagnosed on routine blood tests. Other features include lymphadenopathy, infections and symptoms of bone marrow failure e.g. anaemia, thrombocytopenia. In some patients it is stable and life expectancy is relatively normal but in others it can be rapidly progressive.

Answer 34

Patients are not usually offered treatment for early stage CLL until their disease progresses and some patients may never need treatment. Staging is important as this decides treatment and the staging systems used assess organomegaly and cytopenia Cyclophosphamide – can be given orally or intravenously usually as part of a cyclical regime eg CHOP or in combination with fludarabine. Care must be taken to ensure the patient is adequately hydrated, especially if high doses are used, due to the risk of cystitis and Mesna (Uromitexan®) can be used concurrently with cyclophosphamide to reduce the urotoxic effects. Chlorambucil – is given orally either continuously or intermittently until the disease is stabilised. Treatment is given for several months until a remission is achieved and then reintroduced as needed although patients can develop resistance to the treatment. Fludarabine – purine analogues have improved outcomes in CLL. Fludarabine can be given orally or intravenously as a single agent or in combination with cyclophosphamide for increased effectiveness and duration of response. Rituximab – is useful in combination therapy with fludarabine and cyclophosphamide and improves response rate. It is a monoclonal antibody specifically targeted against CD20 which is found on the surface of B lymphocytes. It binds to the lymphocytes, the immune system then targets these cell and kills them and then these are replaced with normal lymphocytes. Rituximab is approved by NICE for first line treatment of CLL in combination with fludarabine & cyclophosphamide. Ofatumumab – is licensed for the treatment of CLL in patients’ refractory to fludarabine and alemtuzumab (no longer licenced). However in 2010 NICE did not support this due to the lack of robust evidence to support its efficacy and a much higher cost than best supportive care. It use is however supported by the Cancer Drug fund Corticosteroids – are used in patients with bone marrow failure to allow significant recovery of the platelet, neutrophil & haemoglobin levels. Bendamustine – is an alkylating agent which NICE (2011) recommended as an option for the first-line treatment of CLL (Binet stage B or C) in patients for whom fludarabine combination chemotherapy is not appropriate.

Answer 35

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause lymphadenopathy. The malignant lymphomas are divided on the basis of histological appearance into Hodgkin (HL) and non-Hodgkin (NHL) groups.

Answer 36

HL is more prevalent in males than females; it is a rare but curable malignancy. In the UK there are two peaks in the age-specific incidence of Hodgkin lymphoma, one in young people aged 20-25 and another in older adults aged 75-80 years.

Answer 37

80 – 90% of patients with HL present with painless lymphadenopathy usually in the cervical or supraclavicular regions. Enlargement of the spleen or liver and systemic ‘B’ symptoms (fever, weight loss, anorexia & night sweats) can also be presenting symptoms. Blood tests may reveal  Normochromic, normocytic anaemia  Neutrophilia  Eosinophilia  Lymphopenia  Raised lactate dehydrogenase (LDH) and ESR

Answer 38

Treatment is mainly based on the stage and type of lymphoma.  Localised disease – three cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) followed by radiotherapy is the gold standard.  Advanced disease - combination chemotherapy of 6 – 8 cycles of ABVD is established treatment. High risk patients may receive BEACOPP combination chemotherapy (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone). Patients treated with BEACOPP are more difficult to successfully salvage after relapse.

Answer 39

These are a large group of lymphoid tumours, most commonly of B-cell but sometimes T-cell origin. Non-Hodgkin lymphoma is the 6th most common cancer in the UK and there has been a marked increase in the incidence of NHL over the last 50 years. NHL is a diverse group of diseases and may vary from highly proliferative and rapidly fatal diseases to indolent and well-tolerated malignancies. Low grade NHL is relatively indolent, responds well to chemotherapy but can be difficult to cure. High grade lymphomas are aggressive and need urgent treatment but can be curable.

Answer 40

features are quite diverse. They may include: • Lymphadenopathy • Splenic and/or liver enlargement • Oropharyngeal involvement occurs rarely (sore throat, noisy breathing) • Symptoms of anaemia, neutropenia or thrombocytopenia • Night sweats, fever & weight loss

Answer 41

Chemotherapy – CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) has been the gold therapy since the 1970’s and response has been improved by adding rituximab (R-CHOP). CNS prophylaxis – CNS relapse is associated with a very poor prognosis. Conventional chemotherapy doesn’t effectively cross the blood brain barrier so additional chemotherapy agents or intrathecal chemotherapy can be used in high-risk patients. Radiotherapy – can be used alone or in combination with chemotherapy. Refractory/relapsed disease – there are a few other chemotherapy regimens that are used for refractory or relapsed disease with or without rituximab.

Answer 42

This is a malignant disorder of plasma cells, which are derived from B lymphocytes, which secrete monoclonal immunoglobulin. Multiple myeloma is characterised by:  Monoclonal paraprotein in serum and/or urine and related tissue damage  Bone changes leading to pain & pathological features  Excess plasma cells in the bone marrow The paraprotein is an immunoglobulin produced at high levels by a clone of plasma cells. It is mainly a disease of the elderly with a median age at diagnosis of 70 years. Myeloma is more common in men and in Afro-Caribbeans.

Answer 43

Bone pain - especially backache due to vertebral collapse and pathological fractures. Myeloma causes generalised osteopenia and lytic lesions. Features of anaemia - e.g. fatigue, weakness, pallor, dyspnoea, and tachycardia. Recurrent infections - related to deficient antibody production and neutropenia. Bleeding – myeloma protein can affect platelet function and coagulation factors, thrombocytopenia can occur in advanced disease. Renal impairment and/or hypercalcaemia – symptoms include polydipsia, polyuria, anorexia, vomiting, constipation and mental disturbance. They may present acutely unwell and need emergency treatment for acute renal failure, sepsis, spinal cord compression or hyperviscosity.

Answer 44

Myeloma is generally incurable although a few younger patients may achieve long term remission following stem cell transplantation but procedure-related mortality is high. Survival following diagnosis is usually 2 to 5 years depending on the stage at diagnosis. Treatment usually depends on age, older and less fit patients are usually treated with less intensive chemotherapy combinations which can include thalidomide

Answer 45

This involves several courses of intensive combination chemotherapy and corticosteroids to reduce the tumour burden followed by stem cell collection and autologous peripheral blood stem cell transplant.

Answer 46

In elderly patients monthly courses of oral melphalan, prednisolone and thalidomide are usually effective for reducing the tumour burden. Cyclophosphamide can also be used as a single agent. Once a plateau phase is reached (stable levels of paraprotein) the treatment is either stopped until symptoms restart or paraprotein starts to increase or is continued at lower doses as maintenance treatment. The disease tends to be less responsive to chemotherapy at relapse.

Answer 47

Bortezomib is a highly specific proteasome inhibitor. It is recommended by NICE (TA129, TA228) in combination with an alkylating agent and a corticosteroid as an option for the first-line treatment of multiple myeloma if: - high-dose chemotherapy with stem cell transplantation is considered inappropriate and - the person is unable to tolerate or has contraindications to thalidomide It is associated with peripheral neuropathy and thrombocytopenia Lenalidomide is an immunomodulating drug with anti-neoplastic, anti-angiogenic and pro-erythropoietic properties. It is structurally related to thalidomide. NICE (TA171) has approved its use in combination with dexamethasone, as an option for the treatment of multiple myeloma in people who have received two or more prior therapies. The most serious adverse effects of lenalidomide treatment are neutropenia and venous thromboembolism.

Answer 48

 Bisphosphonates are given for bone protection to reduce skeletal complications; they may also improve overall survival.  Patients should drink at least 3L of fluid daily and avoid nephrotoxic medications. Dehydration, hypercalcaemia and infection should be treated promptly to reduce renal toxicity.  Infections should also be treated promptly with a low threshold for antibiotics.  Pain management is important although NSAIDs should be used cautiously due to renal impairment in many patients.

Answer 49

Chemotherapy targets dividing cells and they can work at different stages of the cell cycle. Limitations of chemotherapy include damage to normal cells although selectivity is seen to some tumours as they may be highly proliferative compared to normal cells or are defective in their ability to repair DNA damage. Chemotherapy aims to achieve maximum tumour cell kill balanced against an acceptable amount of toxicity to normal tissues so chemotherapy agents have a narrow therapeutic window.

Answer 50

The main route of administration of chemotherapy is intravenous. It is usually given on an outpatient basis in specialist oncology or haematology outpatient units and requires specially trained chemotherapy nurses to administer. Oral chemotherapy is however becoming increasingly common and is more convenient for patients as it can be taken at home. Some chemotherapy can also be given by other routes including intrathecal, intramuscular, topical and bladder instillation. Most regimens are delivered in cycles with a period of 2 - 4 weeks in between for the patient’s organs, especially the bone marrow, to recover before the next cycle. Most doses of chemotherapy agents are calculated on the patient’s body surface area (m2). There are a number of different equations to do this, such as Du Bois and Mostellar equation. It is important that there is consistency in the equation used and this is approved by the Trust. There are a few exceptions to this e.g. carboplatin is calculated using the Calvert formula. Dose adjustments for impaired renal and liver function may be necessary depending on the chemotherapy agent. Reduction in dose may also be necessary in other circumstances e.g. toxicity previously experienced from a chemotherapeutic agent. Chemotherapy should be prescribed by a competent and trained prescriber and Trusts normally have an approved list. Doctors prescribing chemotherapy should be at least a specialist registrar. Some oncology centres now have pharmacist independent prescribers who review patients and prescribe further courses of chemotherapy. The first cycle of chemotherapy is usually prescribed by the consultant. Extravasation can occur with chemotherapy; this is where the chemotherapy agent leaks into the surrounding tissue instead staying in the intended vessel. This can cause reactions ranging from mild skin irritation to severe reactions which require urgent treatment, sometimes plastic surgery, and may cause tissue necrosis. Administration precautions should be taken to avoid extravasation and nurses are trained to observe for signs of extravasation. Extravasation kits and protocols should always be available where chemotherapy is being administered. Having knowledge of the vesicant cytotoxic agents that are capable of producing tissue necrosis is important.

Answer 51

- System - Side effects - Chemotherapeutic agent likely to cause toxicity - Bone marrow - Neutropenia, Anaemia, Thrombocytopenia - Various but specifically alkylating agents, anthracyclines, taxanes, topoisomerase inhibitors - Gastrointestinal - Diarrhoea, Oral mucositis (Antifolates, fluoropyrimidines) - Nausea and vomiting (various) - Neurological - Peripheral sensory neuropathy (Vinca alkaloids, taxanes) - Ototoxicity (Cisplatin, oxaliplatin) - Renal - Acute renal failure - Cisplatin - Hepatic - Transaminitis - Raltitrexed - Cardiac - Acute or chronic cardiomyopathy (Anthracyclines can only have a finite number of cycles) - Cardiac ischaemic events (Fluoropyrimidines) - Respiratory - Pulmonary fibrosis - Bleomycin - Bladder - Haemorrhagic cystitis - Cyclophosphamide, ifosfamide -Others -Hand-foot syndrome (Infusional 5-fluorouracil, capecitabine) - Anaphylaxis (Taxanes) - Alopecia, fatigue, lethargy, subfertility/infertility, increased risk of second malignancy (Particularly combination chemotherapy containing alkylating agents)

Answer 52

Dukes' A The cancer is in the inner lining of the bowel. Or it is slightly growing into the muscle layer. Dukes' B The cancer has grown through the muscle layer of the bowel Dukes' C The cancer has spread to at least 1 lymph node close to the bowel. Dukes' D The cancer has spread to another part of the body, such as the liver, lungs or bones. Dukes' stage A = T1N0M0 or T2N0M0 Dukes' stage B = T3N0M0 or T4N0M0 Dukes' stage C = any T, N1, M0 or any T, N2, M0 Dukes' stage D = any T, any N, M1

Answer 53

There are 4 stages of tumour size in bowel cancer: T1 means the tumour is only in the inner layer of the bowel T2 means the tumour has grown into the muscle layer of the bowel wall T3 means the tumour has grown into the outer lining of the bowel wall T4 means the tumour has grown through the outer lining of the bowel wall (into another part of the bowel, a nearby organ or structure) There are 3 possible stages describing whether cancer cells are in the lymph nodes: N0 means there are no lymph nodes containing cancer cells N1 means that 1 to 3 lymph nodes close to the bowel contain cancer cells N2 means there are cancer cells in 4 or more nearby lymph nodes There are 2 stages of cancer spread (metastasis): M0 means the cancer has not spread to other organs M1 means the cancer has spread to other parts of the body

Answer 54

Stage 1 means the cancer is in only half of one side of the prostate, or less. It is completely contained within the prostate gland. In the TNM staging system stage 1 prostate cancer is the same as one of the following: T1, N0, M0 T2a, N0, M0 Stage 2 means the cancer is in more than half of one side of the prostate. But it is still completely contained within the prostate gland. In the TNM staging system stage 2 prostate cancer is the same as one of the following: T2b, N0, M0 T2c. N0, M0 Stage 3 means the cancer has broken through the capsule (covering) of the prostate gland. It may have spread into tubes that carry semen (seminal vesicles). In the TNM staging system stage 3 prostate cancer is the same as this: T3, N0, M0 Stage 4 can mean different things, including: The cancer has spread into nearby body organs, such as the back passage or bladder.

Answer 55

* A malignant breast lump is usually painless, but pain can occur. * Nipple symptoms, including change in shape or nipple bleeding, are recognised symptoms as are skin changes, such as tethering or peau d’orange * Axillary lump (unexplained), age >30y * Breast lump (unexplained) with/without pain, age >30y * Breast lump (unexplained) with/without pain, age <30y * Nipple changes of concern (in one nipple only) including discharge and retraction, age >50y * Skin changes that suggest breast cancer

Answer 56

* Overweight/obese * Alcohol * Contraceptive pill or HRT * Inactive lifestyle * Getting older * Family history and inherited genes * Exposure to X-rays and radiotherapy * Diabetes * Dense or Benign breast tissue * DCIS or LCIS (changes in breast tissue) * Late menopause * Started periods at an early age (before 12 years) * Higher levels of hormone IGF-1 * White women * Previous cancer * Height (taller than average) * Not having children or having them later in life

Answer 57

• Mutations in BRCA1 or BRCA2 are linked to an increased risk

Answer 58

* Breast ultrasound * Mammogram is an x-ray of your breasts. * Needle biopsy * Wire guided excision biopsy * Punch biopsy * Breast MRI scan * Fine needle aspiration * Vacuum assisted biopsy

Answer 59

The NHS Breast Screening Programme invites all women aged between 50 and 70 for screening every 3 years

Answer 60

* A cough for three weeks or more * A change in a cough you have had for a long time * A chest infection that does not get better, or getting repeated chest infections * Feeling breathless and wheezy for no reason * Coughing up blood * Chest or shoulder pain that does not get better * A hoarse voice for three weeks or more.

Answer 61

* Smoking * Older age * Passive smoking * Exposure to radon gas. * Exposure to asbestos. * Previous cancer treatment * Lowered immunity (HIV or AIDS) * Family risk * Exposure to air pollution.

Answer 62

• Inherit DNA mutations from parents. But inherited mutations alone are not thought to cause many lung cancers.

Answer 63

* CT scan – a three-dimensional image of the lungs. Sometimes, your specialist may give you a needle biopsy during it, by passing a thin needle through your skin into the lung. * Bronchoscopy and lung biopsy – a thin, flexible tube that goes through your nose or mouth into your windpipe to examine your lungs. They can use it to take a biopsy. * Endobronchial ultrasound scan (EBUS) – a bronchoscopy with an ultrasound. It allows the doctor to look into the lungs and take biopsies of the lymph nodes in the centre of your chest. * Biopsy of neck lymph nodes – a fine needle is used to take biopsies in your neck. This is usually after an ultrasound scan to check the lymph nodes in your neck. * MRI * Ultrasound

Answer 64

There is no national screening programme for lung cancer in the UK. This is because: • it isn't clear that screening can save lives from lung cancer • the tests have risks • they can be expensive Low dose CT scans are being looked as a possible screening test for lung cancer. Tests like this have risks. The lungs are very sensitive to radiation and frequent scans might cause lung damage

Answer 65

* Bleeding from rectum or blood in faeces * A change in your normal bowel habit * A lump that your doctor can feel in rectum or abdomen, more commonly on the right side * A feeling of needing to strain in your back passage, even after opening your bowels * Losing weight * Pain in your abdomen or rectum * Tiredness and breathlessness caused by a lower than normal level of red blood cells

Answer 66

* Eating too much red and processed meat * Eating too little fibre * Obesity * Smoking tobacco * Alcohol * Age * Family history * UC or CD * Previous cancer * Diabetes * Galstones * Acromegaly (pituitary gland produces too much growth hormone and causes an overgrowth of bones) * Benign polyps in bowel * Radiation exposure * H.pylori infection

Answer 67

* Familial adenomatous polyposis (FAP) | * Lynch syndrome, or hereditary non polyposis colon cancer (HNPCC)

Answer 68

* DRE (digital rectal examination) * Flexible sigmoidoscopy * Colonoscopy * CT (computed tomography) colonography * Blood tests (FBC, LFTs, U&Es, Tumour markers) * Tests on your bowel cancer cells

Answer 69

* The screening programmes send a bowel cancer testing kit called faecal occult blood (FOB) every 2 years to men and women between the ages of 60 and 74 years. * New test - faecal immunochemical test (FIT) in 2019. * In some areas, people are invited for a bowel scope test to look at the inside of the lower bowel and rectum. You have this test once, at age 55.

Answer 70

* Early prostate cancer often has no symptoms at all. * Passing urine more often * Getting up in the night * Difficulty passing urine * Urgency to urinate * Leaking urine * Blood in urine or semen (rare) * Erection problems (uncommon)

Answer 71

* Age * Prostate cancer is more common in black-African men * Family history and genes * Overweight/obese * Height (taller increased risk) * High levels of hormone IGF-1 * Previous cancer * Vasectomy * Inflammation of the prostate gland (prostatitis) * Cadmium (type of metal found in tobacco smoke & food)

Answer 72

* The risk increases by up to 5 times in men with the gene BRCA2. And the risk might increase with the BRCA1 gene. These genes also cause breast and ovarian cancers. * Men with a rare syndrome called Lynch syndrome have a higher chance of developing prostate cancer and some other cancers. A change in one of the genes that fixes mistakes in DNA causes this syndrome eg. MSH2 and MLH1 genes.

Answer 73

* Transrectal ultrasound scan (TRUS) * An MRI scan. * Transrectal ultrasound guided (TRUS) biopsy * Transperineal (template or targeted) biopsy * PSA test

Answer 74

There is no national screening programme for prostate cancer because we don’t have a reliable enough test to use. Current tests have risks.

Answer 75

 <3.0ng/ml for men aged 50-59 years  <4.0ng/ml for men aged 60-69 years  <5.0ng/ml for men ≥ 70 years

Malignant Diseases eBook Flashcards

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