Optimizing therapy in advanced-stage Hodgkin lymphoma.

The treatment of Hodgkin lymphoma has evolved continuously since the introduction of extended-field radiotherapy in the 1960s to involved-field and then involved-node radiotherapy, multiagent chemotherapy, combined chemoradiotherapy, risk-adapted and response-adapted modulation, and, most recently, introduction of antibody-drug conjugates and immune checkpoint-blocking antibodies. These changes have translated into progressively increasing cure rates, so that 10-year survival figures now exceed 80%, compared with <50% 40 years ago. The challenge now is how to improve upon success while maintaining, or if possible improving, the quality of life for survivors. Steering between undertreatment, with the risk of avoidable recurrences, and overtreatment, with the risk of unnecessary toxicity, remains complex because control of the lymphoma and the probability of survival are no longer closely linked. This requires trials with long follow-up and continuous reappraisal of the interaction between the illness; the method used to define risk, and the type of treatment involved. One important factor in this is age: outcomes in older patients have not improved at the same rate as those in the population under 60 years of age, reflecting the need for different approaches. Recently, treatment has moved from being primarily risk-based, using baseline characteristics such as anatomical stage and severity of the illness, to a more dynamic approach that takes account of the response to therapy, using functional imaging to make an early appraisal, with the option to modulate subsequent treatment. The results of several trials indicate that this has advantages, but a combination of risk- and response-adaptation is probably ideal.