Is PET-guided exclusion of radiotherapy an appropriate treatment regimen for unfavorable early-stage Hodgkin lymphoma?

The authors investigated the impact of removing radiotherapy (RT) from treatment regimens in patients with early-stage unfavorable Hodgkin lymphoma (HL).

This study concluded that this treatment regimen is just as effective as the standard of care. 

Chemotherapy and consolidation RT is the standard of care for patients with early-stage unfavorable HL. Consolidation RT is meant to kill any cancer cells left after initial treatment. However, RT can have serious side-effects such as decreased thyroid function or heart disease.

Positron emission tomography (PET) is an imaging technique that evaluates treatment efficacy during or after treatment. In patients with advanced HL, PET scanning has been shown to predict in which patients is necessary to give or omit RT. However, in patients with early-stage unfavorable HL, it remains unknown if PET imaging after four cycles of chemotherapy (PET4) can tell the difference between high and low-risk treatment failure and if RT can be safely omitted in certain patients.

This study included 979 patients with early-stage HL. Patients were randomly divided into two treatment groups. Group 1 included 486 patients treated with standard combined treatment involving standard chemotherapy followed by 30 Gy of RT. Group 2 included 493 patients who underwent PET4-guided treatment. This involved the same chemotherapy followed by 30 Gy of RT only in patients with a positive PET4 scan (cancer is present after 4 cycles of chemotherapy). The average follow-up period was 46.2 months.

Survival without cancer worsening after 5 years was similar between group 1 (97.3%) and group 2 (95.1%). Patients who were PET-negative (no evidence of cancer) were 3.03 times more likely to have better survival without cancer worsening compared to those with PET4-positive. 

Common side-effects reported in both treatment groups included leucopenia (low white blood cell counts), low platelet levels, infection and nausea. Serious side-effects were reported in 29% of patients in the combined-modality group and 30% in the PET4-guided treatment group.

The authors showed that PET4-negativity after 4 cycles of chemotherapy can safely omit consolidation RT in patients with newly diagnosed early-stage unfavorable HL.

This study had a rather short follow-up. Late effects from RT can occur even 20 years later and could not be assessed in this trial.