Oncology

 

Prognosis in malignancy

The prognosis for five year survival has not really improved that dramatically for a number of malignancies – the table below^[1] reflects figures up to 1994 for African-Americans in the Unites States (given treatment):

As can be seen, most cancers other than ovary and prostate have really dismal 5 year survival rates once there is distant spread, but patients with liver and pancreas cancers have a poor prognosis even with only local disease.

Hepatoma investigation

Patients usually present with quite advanced disease, with right upper quadrant pain and loss of weight. The liver is usually enlarged, and a mass is sometimes palpable.

In the presence of a characteristic clinical picture, a markedly raised alpha-fetoprotein level is diagnostic. An ultrasound showing a mass is helpful, and the presence of regional or distant spread directs therapy towards palliation, which should include adequate counselling and attention to pain relief and the relief of nausea.

Lung cancer investigation

Pre-test probability increases with increasing age and heavy smoking. Patients usually present with either a mass or an effusion, or both. Rarely, patients with bronchoalveolar cancer can present as an apparent non-resolving pneumonia, and carcinoma of the bronchus can also present as a bronchial or tracheal obstructive lesion, but in that situation also consider oesophageal cancer.

Pleural effusion:

Send 50-100 ml of fluid for cytology. If high index of suspicion, repeat. If a second specimen is negative, yield of further specimens is not high.

Check again that there are no nodes suitable for fine needle aspiration cytology.

Proceed to pleural biopsy EXCEPT if the favoured diagnosis is Kaposi’s, where there is an unacceptably high risk of bleeding.

Lung mass:

• Check for adenopathy carefully, and send aspiration cytology if a node is found. Remember that supraclavicular nodes may be hidden behind the sternocleidomastoid, and don’t forget to feel properly in the axillae.
• Send sputum for cytology, and check personally that the specimen is sputum and not saliva – nine negative specimens are meaningless if they were all saliva.
• Use hypertonic saline nebulisation if the cough is dry.
• Number of specimens. Sputum cytology is not that cheap, and sending more and more specimens gives a lower and lower probability of positivity. Change strategy after five or six negative specimens.
• Evaluate the site of the lesion. If it touches the pleura, it is usually possible to visualise it with ultrasound, and in that case an ultrasound guided fine needle biopsy is the investigation of choice (quicker, and cheaper than bronchoscopy).
• If unable to get an answer from FNAB then consider bronchoscopy.

Leukaemias

Acute myeloid leukaemia

Acute promyelocytic leukaemia (M3), which may present with severe bleeding due to a consumption coagulopathy, used to be considered to have the most severe short term prognosis of all the acute myeloid leukaemias. This picture has changed with the availability of all trans retinoic acid, which transformed this illness into one with a similar prognosis to other leukaemias (not necessarily a better prognosis). Note that not all leukaemics present with a leukocytosis – in some instances the white cell count may be normal or even low, and although the diagnosis may be suspected on the peripheral smear, it needs to be confirmed on bone marrow biopsy.

Initial management entails paying attention to bleeding, anaemia, infection and nutrition.

Anaemia – there is little point in letting the Hb drop too far – it will inevitably drop further in the initial stages of management, so topping up to 10g/100ml makes as much sense as stopping at lower levels, in that about the same amount of blood will be required in the end, but the patient will feel better if the Hb is on average higher.

Bleeding. Monitor the INR/PTT and the platelet count regularly if bleeding occurs and correct with FFP or a pooled unit of platelets as required. Various authorities have different opinions on the precise level of platelet count at which to transfuse – the idea is that devastating bleeds (e.g. subarachnoid) can be avoided by keeping the count above 10-20 000. Clearly, apart from the development of platelet resistance, the risk-benefit is skewed in favour of keeping the count as close as possible to ‘surgically safe’ levels of 60-80 000; however the cost of this is beyond the resources of most institutions. Remember it is a continuum and not a binary variable – there is no certainty that a non-infected patient will bleed even when the count is down to 10 000.

Infection. Much antibiotic therapy is empiric – if febrile or potentially septicaemic, then do a blood culture and start on a cephalosporin-aminoglycoside combination.

Nutrition. This is often an initially neglected part of the management of acute leukaemia – simple issues such as pain on swallowing may limit intake and should be relatively easy to remedy. A fine-bore nasogastric tube may be reasonably well tolerated and will allow some feeding until the stomatitis or oesophagitis has settled.

Definitive therapy

Ideally, all such patients should be referred to a tertiary haematology-oncology centre where they will be considered for bone marrow transplantation. However every now and then there are patients who refuse referral but are prepared to undertake some form of treatment in a more familiar environment (your ward!) Put considerable effort into trying to get these patients to be treated centrally, but if they ultimately still refuse, there is a case to be made for local treatment. At the very least, an informed understanding by yourself of what the process may involve will allow you to counsel the patient and family more productively.

Perspective – all trans retinoic acid

This has made a significant contribution to the management of promyelocytic leukaemia. It is given orally in a dose of 45 mg/m² per day until either remission or 90 days, whichever comes first. Conventional chemotherapy is still usually given as well.

Efficacy of retinoic acid is quite impressive overall with reported three year disease free survival rates of 75% for retinoic acid given as both induction and maintenance, and 60% for induction with no maintenance, versus a rate for standard induction chemotherapy followed by observation of 18%^[2].

Acute lymphoblastic leukaemia

Patients can be quite ill on presentation, with bleeding, high fever and pallor.

Suspect the diagnosis from the FBC and smear, but confirm it on marrow biopsy.

Definitive therapy

The same basic considerations apply as for AML – tertiary referral, assessment for transplantation, and if this isn’t done, or while awaiting it, chemotherapy:

Remission induction with a combination of vincristine, daunorubicin, prednisone, asparaginase.

CNS prophylaxis –intrathecal methotrexate and CNS irradiation.

Consolidation – a few further courses of the chemotherapy part of induction at 6 weekly intervals

Maintenance – two years of treatment with vincristine and prednisone monthly, methotrexate weekly and mercaptopurine daily.

Chronic myeloid leukaemia

This often presents with malaise, weight loss and anaemia. Splenomegaly is common and can be massive. The WCC is often >100 000, and more than 95% of patients are Philadelphia chromosome positive. Treatment is ideally by oncologists or haematologists, but one can use hydroxyurea 500mg – 2g daily titrated against the white cell count. Do not run the WCC too low, especially if visits for FBCs are erratic. Running the count at 10-15 000 is very reasonable and is safer than counts of 3 – 4 000. There may be significant tumour lysis on initiation of therapy, so start all patients on allopurinol 300 mg per day for a few days first and use it for a few weeks until the tumour burden is reduced. You do not need to continue it long-term.

Perspective – imatinib

Imatinib is a tyrosine kinase inhibitor which produces more rapid and complete cytogenetic response in CML than conventional therapies^[3]. Although formal long term survival information is still awaited, it has been estimated to contribute an extra four years to survival; the relevance of this is that the medication is available in the public sector as part of a donation programme.

Chronic lymphoid leukaemia

This presents with enlarged lymph nodes (can be very big). Diagnosis is by either lymph node biopsy or bone marrow biopsy. There is sometimes an associated autoimmune haemolytic anaemia. Sometimes no active treatment is required. Isolated regional nodes causing symptoms may respond to radiotherapy. For more generalised disease in an individual with constitutional symptoms, use chlorambucil 4 – 8 mg per day. (It comes as a 2 mg tablet.)

Lymphoma

Diagnosis is made based on lymph node excision biopsy in patients with symptomatic adenopathy. It is important that the entire node be removed and sent for histology, as tiny samples are difficult to interpret. Hodgkin’s lymphomas have Reed-Sternberg cells and non-Hodgkin’s don’t. Treatment for early stages of the former is radiotherapy, and chemo for more advanced disease. Mild forms of non-Hodgkin’s can be watched in consultation with an oncologist, and more severe forms can be treated with cyclophosphamide or chlorambucil. Refer if possible.

Multiple myeloma

Some patients may prefer, for logistic or other reasons, not to be treated in an oncology unit, and as management is reasonably straightforward, it is acceptable to look after such individuals in outpatients, but if in any doubt ask for advice.

It is not appropriate to treat Stage 1 patients (Hb > 10, normal calcium) but most patients present with Stage 3 disease (HB < 8.5, hypercalcaemia). Consider treatment if there is bone pain, hypercalcaemia, renal failure or anaemia.

Attend to hypercalcaemia. (See separate section.)

If renal function is normal, start on allopurinol 300 mg /d for 2-3 days before commencing chemotherapy, and continue it for a fortnight after the first dose of the initial cycle of therapy.) Give:

• prednisone 1.5 mg/kg/day (or 60 mg/m2) for four days (e.g. 90 mg/d for 4 days) and
• melphalan 0.15 mg/kg/day (or 10 mg/m2) for four days (e.g. 9 mg/day for 4 days).
• Repeat the cycle every six weeks.

Monitor the CRP and protein electrophoresis (quantitative) at 6 monthly intervals or at 3 monthly intervals if looking for a plateau to support stopping treatment. If the patient has responded well, it is probably reasonable to stop therapy after 6 months, as ongoing therapy doesn’t seem to improve prognosis.

Monitor the FBC at each visit (monthly or six-weekly) before giving a new course of treatment. Delay therapy and ask for advice if the WCC is <3.5.

If the Hb is falling, it is either because of too aggressive treatment or marrow infiltration, so stop treatment and check the Hb after two weeks; if it doesn’t improve, then consider repeating the marrow unless the electrophoresis strongly suggests that the disease is out of control. Some patients are just folate deficient.

Document the blood results and the doses used on a flow sheet, so that someone else seeing the patient for the first time can get some idea of what is going on.

Suggested minimum dataset for myeloma follow up:

At each visit:	Three to six monthly:
Date	Weight	Hb	WCC	Plt	CRP	Ca	Alb	Electrophoresis.

Perspective – diagnostic testing in multiple myeloma.

Assuming that the alternative diagnosis is another malignancy, serum immunoglobulins had a sensitivity of 95% (spec 99%, LR+ 95 LR- 0.1) for detecting myeloma, contrasting with bone marrow sensitivity of 90% but specificity of only 50% (LR+ 1.8, LR- 0.2. ^[4])

Hypercalcaemia in malignancy

• Treating the cause is best.
• Stop thiazide diuretics, and rehydrate. If the patient’s cardiovascular system can tolerate it, give normal saline 1 litre 8 hourly I.V. and encourage oral fluids
• Aggressive saline diuresis is fraught with difficulty unless you can watch the process carefully yourself. Remember that the saline must come first – don’t give the furosemide and then the fluid…
• Multiple myeloma is a common aetiology, and starting treatment with prednisone and melphalan is quite effective and quick.
• Use of a bisphosphonate is effective but more expensive and still takes a few days to bring the levels down. Pamidronate in a dose of 30 mg IV in 500 ml saline over 6 hours is available, but should be primarily offered to those where there is a reasonable chance of doing something about the underlying malignancy. Lowering the calcium in a terminally ill person with disseminated disease is seldom helpful.

1. American Cancer Society, United States, 1989–1994. Surveillance Research, 1998. Source: NCI Surveillance, Epidemiology, and End Results Program, 1998. ↑

2. Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retinoic acid in acute promyelocytic leukaemia. N Engl J Med. 1997;337:1021-8. ↑

3. Reed SD, Anstrom KJ, Ludmer JA, et al. Cost-effectiveness of imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer. 2004;101;2574-83. ↑

4. Reilly BM, Clarke P, Nikolinakos P. Easy to see but hard to find. N Engl J Med. 2003;348:59-64. ↑

5. Bale S, Tebbie N, Price P. A topical metronidazole gel used to treat malodorous wounds. Br J Nurs. 2004;13:4S-11S. ↑

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