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Trying to spare people radiotherapy by using a clear scan after two rounds of chemotherapy cost them about seven in a hundred in disease control, so the radiotherapy stayed.
Radiotherapy in early Hodgkin lymphoma is the main cause of the second cancers and heart disease that the Dutch late-effects cohorts measured decades later, so omitting it in people who respond quickly has been the field's most wanted de-escalation. HD16 tested it directly. 1,150 patients aged 18 to 75 with newly diagnosed early-stage favourable Hodgkin lymphoma were randomised to standard combined-modality treatment of two cycles of ABVD with 20 Gy of involved-field radiotherapy, or to a positron emission tomography-guided arm in which the radiotherapy was omitted after a negative scan.
Among the 628 patients with a negative scan treated per protocol, five-year progression-free survival was 93.4 per cent (95 per cent confidence interval 90.4 to 96.5) with combined-modality treatment and 86.1 per cent (81.4 to 90.9) with chemotherapy alone, a difference of 7.3 points (1.6 to 13.0) and a hazard ratio of 1.78 (1.02 to 3.12). Five-year overall survival was 98.1 and 98.4 per cent. Among the 693 patients assigned to combined-modality treatment, a positive scan after two cycles predicted worse progression-free survival, 88.4 against 93.2 per cent (p = 0.047), and the gap widened to 93.1 against 80.9 per cent (p = 0.0011) when the more common liver threshold of Deauville score 4 was used.
The trial is a clear negative for the de-escalation it tested and a clear positive for the prognostic value of the interim scan. It is also the reason that the current attempts to drop radiotherapy, such as RADAR, change the chemotherapy as well rather than relying on the scan alone.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
1,150 enrolled.
95 per cent confidence interval 90.4 to 96.5 · 81.4 to 90.9
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival at 5 years, scan-negative patientsprimary | Chemotherapy with radiotherapy | - | 93.4% | 1.78 (1.02 to 3.12) | - | link |
| Chemotherapy alone | - | 86.1% | ||||
| Overall survival at 5 years | Chemotherapy with radiotherapy | - | 98.1% | - | - | - |
| Chemotherapy alone | - | 98.4% |
Radiotherapy cannot be omitted in early-stage favourable Hodgkin lymphoma on the basis of a negative interim scan without a clinically relevant loss of tumour control. The scan is better at identifying who needs more than at identifying who needs less.
The interim scan should be used to intensify treatment in early Hodgkin lymphoma, not to withhold radiotherapy. The 99.0 per cent five-year progression-free survival in the scan-negative favourable group with combined-modality treatment is the number any radiotherapy-sparing strategy has to match.
The reason cardiac surveillance belongs in Hodgkin lymphoma survivorship care, the reason smoking cessation is a specific intervention for this group rather than general advice, and part of the reason modern protocols try to limit both mediastinal radiation and cumulative anthracycline dose.
The reason every current Hodgkin lymphoma trial is a de-escalation trial, and the reason survivors need lifelong surveillance rather than discharge at five years. It is also a warning about assuming that a gentler protocol is a safer one until a cohort has been followed long enough to say.
Shares Andreas Engert, Peter Borchmann, German Hodgkin Study Group, Deauville five-point scale and the tag lymphoma-evidence.
Shares Andreas Engert, Peter Borchmann, German Hodgkin Study Group, Deauville five-point scale and the tag lymphoma-evidence.
Shares Deauville five-point scale, ABVD, BEACOPP and BrECADD (Hodgkin lymphoma regimens), Dacarbazine, Bleomycin and the tag lymphoma-evidence.
Shares Deauville five-point scale, ABVD, BEACOPP and BrECADD (Hodgkin lymphoma regimens), Dacarbazine, Bleomycin and the tag lymphoma-evidence.
Shares Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk, Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, Early-stage classical Hodgkin lymphoma (stage I to II), Radiotherapy and the tag lymphoma-evidence.
Shares Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk, Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma, Early-stage classical Hodgkin lymphoma (stage I to II), Radiotherapy and the tag lymphoma-evidence.
Shares Positron emission tomography-guided treatment in early-stage favorable Hodgkin lymphoma: final results of the international, randomized phase III HD16 trial by the German Hodgkin Study Group, Deauville five-point scale, Early-stage classical Hodgkin lymphoma (stage I to II), PET/CT and the tag lymphoma-evidence.
Shares Survivorship and late effects are neglected, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Doxorubicin, Toxicity and quality of life are undervalued and the tag lymphoma-evidence.