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		Relapse

Relapse

In most instances, childhood cancer will respond to initial treatment and the disease can be controlled. When this response is sufficiently marked so that all evidence of the cancer (tumour or leukaemia) is gone, the term "complete remission," often abbreviated to "remission," is used. This is regarded as first step in achieving a cure of the cancer. However, it is necessary to continue therapy beyond this point in order to eradicate microscopic residual cells that are not detectable by currently available methods. The duration and the intensity of this treatment, called "maintenance" in leukaemia or "adjuvant" in solid tumours, is determined by the specific type and extent of the original cancer.

If the cancer or leukaemia recurs, whether at the same place or other places in the body, the term "relapse" is used. There are many factors that determine the appropriate way of dealing with relapse. However, it is fair to say that relapse is always an adverse (bad) event, and is viewed as a major setback in the potential for cure.

Although every child is different and the approach will vary depending on individual circumstances, some general principles regarding relapse can be discussed in this document. The first thing to consider is the range of factors that determine the severity of this event (how bad?). These include:

• What was the initial treatment and how intensively was it delivered? This will tell us something about the relative resistance of the cancer cells, as well as potential options available as a second line treatment. Variables such as the prior chemotherapy combination, whether radiotherapy has already been tried and whether very intensive approaches such as bone marrow transplantation have been included, all impinge on the available options at relapse.
   
• The timing of relapse is very important. In general terms, the longer it is from initial diagnosis the more likely it is that at least a second response can be expected. Furthermore, whether relapse occurs while still receiving chemotherapy or sometime after ceasing it, also make a difference. Relapse which occurs while receiving some of the best available drugs will be more difficult to handle than one that occurs sometime after the treatment has been completed. Conceptually, any relapse would suggest that the cancer cells are, at least to some extent, resistant to the drugs (and possibly irradiation) that have been given to that time. There often are second line drug combinations available, but the fact that they are second line suggest that they are either not as good as the first line or may have more side effects.
   
• The place where relapse occurs is also an important factor. In solid tumours the relapse may occur at the same site as the original tumour, as well as at one or more other sites in the body. Generally, any one site is better than several. The capacity to operate, give radiotherapy, or expect a response to new chemotherapy drugs would all be affected by where the relapse occurs and what has been given previously. In leukaemia, the most common relapse is in the bone marrow, which is like the original disease coming back again. Sometimes, relapse can occur in special sites such as the brain and spinal cord or the testes or lumps in unusual places. The approach to each of these circumstances is different and the chance of achieving further control and possibly cure, varies accordingly.

Given the many variables that may be present for each patient, decisions regarding appropriate choices for each individual family can only be made after the above issues are determined and discussed. The questions that your doctor will be evaluating and presenting to you include the following:

• What treatment combination can achieve a response after relapse?
• What are the possibilities of achieving a second remission?
• How long are response or remission likely to last?
• Is cure still a goal and if so how likely?
• What side effects are likely to be encountered in the various available approaches?
• What will happen if no treatment is offered and the cancer is allowed to progress unchecked?
• If cure is only a small possibility, what else is available to control the manifestations of the cancer and offer quality of life?

In considering all these questions, one would evaluate all the factors discussed in the early part of this document and rely on experience both within our institution and from children's cancer centres all over the world. There are numerous scientific articles being written constantly about the battle to improve salvage treatment after relapse. The decision for each individual child will be determined by both the factual information available from your doctor and also the views and feelings of the family when confronted with this information. However, one thing remains central to this: the family and child can only come to a reasonable decision if they have had the opportunity to hear and to understand the options available to them. The purpose of subsequent therapy needs to be carefully considered. It may be possible to decide clearly whether the treatment is being given "with curative intent" or whether quality of life is the prime consideration and cure is not expected. If the information available or the emotional status of the family is such that this decision cannot be reached, it is possible to commence intensive therapy and be further guided by the initial response that is documented.

It is apparent from the above discussion that a range of options are available for children who relapse with cancer. In general terms, the possibility of cure after relapse is always less than it was at initial diagnosis. It may be possible to predict the odds of response and of possible cure according to previous experience in similar circumstances. In some situations, the chance of cure after relapse is close to zero and it is important to acknowledge that. It would be unusual to offer no treatment, because the potential manifestations of unchecked cancer growth will affect quality of life more than some treatment options. Therapy may consist of measures aimed specifically at relieving discomfort and other symptoms, an approach called "palliative treatment". At the other end of the range of options, it may be appropriate to try the most intensive combination of drugs, radiation, operations and bone marrow transplantation. The issues relating to bone marrow transplantation are covered in other sections of the Patient and Family Information Book. Its potential role for relapsed patients depends entirely of the many factors described above. When transplantation is considered to be a possible option for treatment of relapse, there are a number of potential sources of bone marrow: siblings, other family members, unrelated donors from a registry or the patient's own bone marrow collected and frozen down. One principle remains, regardless of the intensity and complexity of treatment being offered in relapse: if a cure is to be possible, a second remission must first be achieved.

The side effects expected depend largely on the intensity with which treatment is delivered. Both sides of the equation need to be considered before a decision is taken. As a general principle, it is necessary to accept higher risks in terms of side effects when offering relapse treatment than when beginning treatment at initial diagnosis. Sometimes, new treatments become available for which there is no established experience. These treatments are referred to as "experimental" and they are tried in a context of a "clinical study". If your child is given the opportunity to enrol in a clinical study this should be clearly known to you, as should all other alternatives available. Importantly, whether you participate in a clinical study or you do not, will have absolutely no effect on your relationship with your doctor and the other professionals in the Unit, or our commitment to caring for your child and the family.

If a family chooses to pursue palliative care, it means the emphasis is primarily on optimal quality of life and intensive attempts at achieving further remission are not being pursued. While this is often a very difficult decision to reach, at times it becomes apparent that it is the only reasonable option. Most importantly, the dedication and caring by all our staff that goes into the management of a child and family who are receiving palliative care is as great if not greater than when cure of the cancer is the primary goal. The intensity of treatment is replaced by intensity of support with all the resources available to our Unit. Many members of the health care team are involved in delivering this support, and include input from health professionals closer to home. Local liaison and home care are covered in another chapter of the Patient and Family Information Book.

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