Loading
Advanced Hodgkin lymphoma can be treated with a gentler combination that fewer people are cured by first time, or a harder one that cures more but leaves more lasting harm. Scanning after two cycles, and the newer escalated regimens, have narrowed the gap between the two rather than settled the argument.
**What the choice used to be.** For thirty years the question in advanced Hodgkin lymphoma was whether to give ABVD, which most people get through without being admitted, or escalated BEACOPP, which controls the disease in more people first time and carries more infection, more infertility and more second cancers. Because Hodgkin lymphoma mostly affects people in their twenties and thirties and most of them are cured, the argument was never only about the first two years.
**What the interim scan changed.** RATHL registered 1,214 people with newly diagnosed advanced classical Hodgkin lymphoma, gave two cycles of ABVD and scanned. 937 of the 1,119 scanned (83.7 per cent) had a negative scan; those people were randomly assigned to continue ABVD or to drop the bleomycin. At a median follow-up of 41 months, three-year progression-free survival was 85.7 per cent with ABVD and 84.4 per cent without the bleomycin, overall survival 97.2 and 97.6 per cent, and respiratory adverse events were more severe in the group that kept the bleomycin. The 172 people with a positive scan were escalated to BEACOPP; 74.4 per cent had a negative third scan, and their three-year progression-free survival was 67.5 per cent. The practical change is that the decision is no longer taken once, before anything is known: most people are treated gently and only the minority whose scan is still positive are escalated.
**What the newer escalated regimen changed.** HD21 randomised 1,500 people under 61 with newly diagnosed advanced-stage classical Hodgkin lymphoma to escalated BEACOPP or to BrECADD, both guided by the scan after two cycles. Treatment-related morbidity, a co-primary endpoint, was significantly lower with BrECADD, in 312 of 738 people (42 per cent) against 430 of 732 (59 per cent), a relative risk of 0.72. The escalated approach became less harmful rather than less escalated.
**What the late harm actually is, in numbers.** The two Dutch cohorts are the reason this decision is weighed over decades. Among 3,905 people who survived at least five years after Hodgkin treatment given between 1965 and 2000 at ages 15 to 50, 1,055 second cancers occurred in 908 people over a median 19.1 years, 4.6 times the rate expected from the general population, still 3.9 times higher 35 or more years on, and the cumulative incidence of a second cancer at 40 years was 48.5 per cent. Among 2,524 people treated before the age of 51 between 1965 and 1995, the 40-year cumulative incidence of cardiovascular disease was 50 per cent, with mediastinal radiotherapy and anthracycline chemotherapy each carrying their own increase. Both cohorts were treated with the radiotherapy fields and doses of their era, which are larger than anything used now, and the second-cancer paper's own finding was that the risk of second solid cancers was no lower in the most recent period it studied.
**What the fertility difference is, in numbers.** In the German HD13 to HD15 survivor analysis of 1,323 people, hormone levels tracked the intensity of treatment. After six to eight cycles of escalated BEACOPP, menstrual activity depended strongly on age: 82 per cent in women under 30 and 45 per cent in women of 30 or more, and 34 per cent of women aged 30 or over had severe menopausal symptoms, three to four times more often than expected. Male survivors had mean testosterone in the normal range and reported no increase in symptoms of low testosterone. The fertility conversation therefore belongs before the first cycle, not after it.
**What is not settled.** Which of the two modern answers is better. The United States standard after SWOG S1826 is nivolumab with AVD; the German and much of the European standard after HD21 is PET-guided BrECADD. No trial has compared them. Facet B's rows set out each.
Showing the technology this term belongs to: PET-adapted (response-adapted) therapy.
Shares ECHELON-1, RATHL, PET-adapted (response-adapted) therapy, Advanced-stage classical Hodgkin lymphoma (stage III to IV).
Shares Fertility preservation before lymphoma treatment: a decision with a deadline in days, GHSG HD21, Late effects of Hodgkin lymphoma treatment, and the follow-up that answers them, Oncofertility and fertility preservation.
Shares RATHL, GHSG HD21, SWOG S1826, Advanced-stage classical Hodgkin lymphoma (stage III to IV).
Shares ECHELON-1, GHSG HD21, SWOG S1826, Advanced-stage classical Hodgkin lymphoma (stage III to IV).
Shares RATHL, PET-adapted (response-adapted) therapy, Advanced-stage classical Hodgkin lymphoma (stage III to IV), Hodgkin lymphoma.
Shares ECHELON-1, GHSG HD21, SWOG S1826, Advanced-stage classical Hodgkin lymphoma (stage III to IV).
Shares Secondary malignancy (therapy-related cancer), Deauville score and PET-adapted therapy, Advanced-stage classical Hodgkin lymphoma (stage III to IV), Hodgkin lymphoma.
Shares Fertility preservation before lymphoma treatment: a decision with a deadline in days, After Hodgkin lymphoma: the late effects, and the screening that follows them, PET-adapted (response-adapted) therapy, Cardiotoxicity (LVEF decline, cardiomyopathy).