What therapy options are there? Therapy is aimed at cure with least morbidity (i.e. damage to the patient). As most cases of Hodgkin’s disease are curable, so this last caveat is most important.
Early stage Hodgkin’s disease, such as stage 1A of the neck glands can be cured by the local application of moderate dose radiotherapy to the nodal region in most cases. The chance of cure may be enhanced by irradiating all the nodes above the diaphragm(in a technique called the mantle technique) such that the next nodes that will be involved by this disease that progresses in the logical method outlined above are treated, to sterilise any early microscopic disease there. Also, if chemotherapy were to be applied to the same patients as well as the radiotherapy, it would probably move the first time cure rate up from 85% to almost 100%.
However, to deliver both wide field radiotherapy and chemotherapy to all patients with stage 1a disease would over-treat the vast majority and such combined modality therapy has toxicity for the patients that one would want to avoid.
Therefore, in most cases, these patients with stage 1A disease will receive radiotherapy alone and a careful watch policy. It has been shown that such a policy will not prejudice their overall cure rate (i.e. chemotherapy introduced for those minority of patients who later relapse salvages as many as to bring the overall total of cures up to those of a primary chemo-radiotherapy programme). This is an important concept to understand: viz. that in this disease we do not always need to reach for the heaviest guns first – an unusual concept and one that is not generally applicable to most common cancers.
For stage 2 Hodgkin’s disease, where the disease is small bulk and there is only a small amount of disease in two adjacent nodal groups, a primary radiotherapy strategy is also attended by a high first time cure rate and no compromise to overall survival by omitting primary chemotherapy. Almost everyone would use a mantle type treatment strategy to encompass all the lymph node groups at risk on that side of the diaphragm rather than just irradiating those groups of nodes that had been shown to be involved on scanning. In most cases in the UK, a neck presentation is found to be associated with involvement of the chest nodes and often the size of the chest nodal mass is considerable.
It has been shown that where there is a sizeable chest mass, the chance of first time cure by radiotherapy alone is considerably less than in other stage 2 cases and this fact and the fact that considerable more lung is irradiated to the therapeutic dose when the chest nodal mass is large, so alternative strategies have been devised.
The alternative strategy is one of primary chemotherapy to shrink the mass of Hodgkin’s disease right down to minimal size and then to deliver the radiotherapy (often to a lesser dose in view of the good initial response to the chemotherapy).
For higher stage cases, the use of chemotherapy becomes more routine. It is one of the great success stories of modern times that combinations of cytotoxic chemicals can cure Hodgkin’s disease and the current controversies relate to the optimal regime. For example, one of the most tried and tested curative regimes (MOPP and variants thereof) is highly effective at curing patients but tends to sterilise the patients and the same group of constituent drugs that tend to sterilise (the alkylating agents) also combine with radiotherapy, if used, to increase the risks of late second cancers (the late development of a new cancer in a patient cured of one cancer type and caused by the previous cancer treatment).
Another highly effective curative regime is ABVD which does not contain any alkylating agent but does contain an anthracycline drug which is cardiotoxic after a high cumulative dosage has been administered, and if chest radiotherapy is used together with ABVD then it is likely to lead to cardiac dysfunction.
These are important considerations in a population of young patients for whom one is expecting cure and the issue of maximising the chances of first time cure whilst minimising the risks of therapy is as heatedly argued in this disease as in any other in Oncology at present. This controversy has given rise to many new therapeutic attempts to obviate these side effects/complications of therapy. For example, many now use ‘hybrid’ chemotherapy for several reasons. Hybrid chemotherapy rotates different active combination drug regimens around such that the disease is exposed to more agents and, in theory is less likely to develop drug resistance to any one, and, with the above toxicity considerations in mind, reduces the patient to cumulative exposure to any one drug type. Furthermore, in a chemo-radiotherapy regimen, where the chemotherapy is nowadays almost always used first, the radiotherapy is reduced in dose and extent (e.g. more cardiac protection) where the patient’s disease has responded well to the primary chemotherapy.
In general, where the disease is very extensive, then the programme is very heavily biased in favour of chemotherapy whereas for more localised disease the use of radiotherapy is more common. In general terms, where chemotherapy is used alone, the first time cure rate is of the order of 67% overall, with the earlier stage patients doing better than this overall figure and the stage 4 patients with liver and bone marrow disease doing worse.
