Oncological emergencies: clinical importance and principles of management.

Oncological emergencies are common conditions associated with significant morbidity and mortality. Delay in diagnosis and treatment can result in unfavourable outcomes. Cancer itself, cancer-related hormones or cytokines, or treatment effects can cause emergency problems. Febrile neutropaenia, frequently associated with chemotherapy, can lead to life-threatening conditions. Treatment requires systematic evaluation and early empirical antibiotics. Hypercalcaemia of malignancy is the most common metabolic emergency in cancer patients. Non-specific clinical features may cause delay in diagnosis and increase morbidity and mortality. Treatment includes active fluid resuscitation, diuretics and intravenous bisphosphonates. Superior vena cava syndrome is usually caused by external compression. Computerised tomography is useful to confirm diagnosis, evaluate the extent of disease and guide invasive tissue diagnosis. Treatment and prognosis depend on the underlying malignancies. Spinal cord compression is a true emergency due to risk of permanent neurological impairment. Localised back pain is the most common presenting symptom while late presentation of neurological deficit is associated with irreversible outcomes. Magnetic resonance imaging is the investigation of choice. Treatment includes corticosteroids, radiotherapy and/or decompressive surgery.

Treatment of established breast cancer in post-menopausal women: role of aromatase inhibitors.

Endocrine therapy plays a crucial and historically important role in the treatment ofwomen with hormone-responsive breast cancer. Tamoxifen has been the standard endocrine treatment for advanced and early-stage breast cancer for almost three decades. However, patients receiving tamoxifen may either fail to respond or develop disease recurrence following completion of therapy. The aromatase inhibitors (Als) have become the new and alternative modalities of endocrine treatment for post-menopausal women with oestrogen receptor-positive breast cancer, as a result of promising data from randomised trials in metastatic and locally advanced breast cancers. Recently, the results from several large, randomised, controlled adjuvant trials have provided further evidence that the use of Als, either as initial treatment or sequentially after tamoxifen, improves disease-free survival and, in certain patients, overall survival. With relatively short-term follow-up, the use of Als has been shown to be safe and welltolerated. Nevertheless, some detrimental adverse effects, particularly skeletal-related events or cardiovascular disease, remain important issues of concern and warrant continued monitoring and follow-up. The optimal use of Als, the appropriate timing of treatment, and the superiority of individual agents are under investigation. Use of Als in women with chemotherapy-induced amenorrhoea should be cautious due to the possibility of return of ovarian function. Cost-effectiveness and quality of life remain issues of interest since the high and ever increasing incidence of breast cancer has contributed to significant healthcare costs and patients with breast cancer following appropriate treatment are living longer but not necessarily being cured of their diseases.

Neoadjuvant chemotherapy in women with large and locally advanced breast cancer: chemoresistance and prediction of response to drug therapy.

Patients with large and locally advanced breast cancer (LLABC) present with a therapeutic challenge and undergo multimodality treatment. Many such patients receive neoadjuvant chemotherapy (NAC) prior to surgery. However, a number of these patients do not respond well to NAC and only a percentage (usually less than 30%) obtains a complete or optimal response. A range of mechanisms are believed to be involved in this chemoresistance, including ATP binding cassette (ABC) transporter overexpression, dysregulation of apoptosis and possibly increased numbers of cancer stem cells. The chemoresistant processes may be due to more than one mechanism. The ability to predict a response to NAC would be beneficial, targeting expensive and toxic drug treatment to those likely to respond and providing a therapeutic strategy for further post-operative chemotherapy. Currently, many biomarkers have been studied with a view to establishing a predictor of response. However, no single biomarker appears to be effective. Genomics is a novel biotechnological process which is being used to predict response to drug therapy; this work is currently at an early stage of development

Vaccination therapy in malignant disease.

Improvement in survival among patients with early malignancy is well established in various cancers. However, long-term survival in those with advanced malignancy has changed little and this poses a major therapeutic challenge to clinicians. Anti-cancer immunotherapy is a novel approach, which is still experimental, but offers a new therapeutic strategy. In this review, we discuss the basic immunological interplay between the host immune system and the tumour, mechanisms of anti-tumour immune responses induced by immunotherapy and key in vivo pilot studies of active specific immunotherapy in various sold cancers, carried out during the last five years.

Multimodality treatment in the management of locally advanced breast cancer.

Forty-two patients with locally advanced breast cancer were treated with multimodality therapy comprising neoadjuvant chemotherapy (cyclophosphamide, vincristine, doxorubicin and prednisolone) and radiotherapy to the breast and lymph-draining areas, followed by tamoxifen and then selective surgery. The objective response rate (UICC criteria) of the primary tumours to chemotherapy alone was 72%, which increased to 83% following radiotherapy. The patients have been followed up for 13-56 months and the probability of local control at 36 months was 0.83. The probabilities of distant disease-free survival and overall survival were 0.50 and 0.65 respectively, at 36 months. However, if the patients' breast cancers had shown a response to chemotherapy/radiotherapy then the distant disease-free survival and overall survival of these subgroups of patients were 0.61 and 0.83 respectively, at 36 months. Toxicity included nausea, vomiting, alopecia, and peripheral neuropathies (two patients), but with no episodes of severe infection or bleeding. This multimodality therapy has achieved good local control and satisfactory overall and distant disease-free survivals with excellent patient compliance.