A ’sanctuary site’ is the term used to indicate that metastatic disease has involved a site that is not accessible to conventional drug therapy. An example of this is leukaemic infiltration of the meninges in children with acute lymphoblastic leukaemia. Because of the blood-brain barrier, agents such as vincristine and prednisolone do not enter the subarachnoid space in sufficient quantity to eliminate all the leukaemic cells, and are therefore ineffective in preventing the development of meningeal infiltration. In order to treat these cells, intrathecal chemotherapy and/or cranial irradiation are required for patients at risk.

A measurable response to treatment can serve as a useful early surrogate marker when assessing whether to continue a given treatment for an individual patient.

Response to treatment can be subjective or objective. A subjective response is one perceived by the patient in terms of, for example, relief of pain and dyspnoea, or improvement in appetite, weight gain or energy. Such subjective response is a major aim of most palliative treatments. Quantitative measurements of these subjective symptoms form a part of the assessment of response to chemotherapy, especially in those situations where cure is not possible and where the aim of treatment is to provide prolongation of good-quality life. In these circumstances, measures of quality of life enable an estimate of the balance of benefit and side-effects to be made.

Objective response to treatment is measured either as a complete response, which is a complete disappearance of all detectable disease clinically and radiologically or partial response, which is conventionally defined as more than a 50% reduction in the size of the tumour. The terms used to evaluate the responses of tumours are given in Box 9.2. The term ‘remission’ is often used synonymously with ‘response’ which if complete means an absence of detectable disease without necessarily implying a cure of the cancer.

When cure is no longer possible, palliation, i.e. relief of tumour symptoms and prolongation of life, is possible in many cancers in proportion to their chemo- and radiosensitivity. There is on average a 2-18 months prolongation in median life expectancy with treatments for solid tumours and up to 5-8 years for some leukaemias and lymphomas, with those with the most responsive tumours experiencing the greatest benefit. The development of more effective chemotherapeutic drugs and better supportive care such as antiemetics has done much to reduce the side-effects of chemotherapy and to improve the cost/benefit ratio for the patient receiving palliative treatment. In addition, through early assessment during treatment, it is possible to stop if there is no evidence of benefit within 6-8 weeks of starting, so as to minimize exposure to toxic and unsuccessful treatment.

For most solid tumours local control is possible but not sufficient for cure because of the presence of systemic (microscopic) disease, while haematological cancers are usually disseminated from the outset. Improvement in the rate of cure of most cancers is thus dependent upon earlier detection and effective systemic treatment. The likelihood of cure of the systemic disease depends upon the type of cancer, its chemo-/hormonal sensitivity, and tumour bulk (microscopic or clinically detectable). A few rare cancers are so chemosensitive that even bulky metastases can be cured, e.g. leukaemia, lymphoma, gonadal germ cell tumours, and choriocarcinoma. For most common solid tumours such as breast and colorectal cancer, there is no current cure of bulky (clinically detectable) metastases, but micrometastatic disease treated by adjuvant chemotherapy (see below) after surgery can be cured in 10-20% of patients.

Advances in medical treatment over the past three decades have led to a huge increase in the number of patients living with immunodeficiency states. Cancer chemotherapy, the use of immunosuppressive drugs and the world-wide AIDS epidemic have all contributed to this. The presentation may be very atypical in the immunocompromised patient with few, if any, localizing signs or symptoms. Infection can be due to organisms which are not usually pathogenic, including environmental bacteria and fungi. The normal physiological responses to infection (e.g. fever, neutrophilia) may be diminished or absent. The onset of symptoms may be sudden, and the course of the illness fulminant. A high index of suspicion for infections in people who are known to be immunosuppressed is required. These patients should usually be given early and aggressive antibiotic therapy without waiting for the results of investigations. Samples for culture should be sent before starting treatment, but therapy should not be delayed if this proves difficult. The choice of antibiotics should be guided by the likely causative organisms: these are shown in Box 2.4.