Risk-adapted therapy.

Top Line: Radiation for Hodgkin lymphoma is one-size-fits-all, right?

The Study: Radiation pretty clearly reduces the risk of disease recurrence or progression in patients with early stage Hodgkin lymphoma (HL). Whether that benefit is worth the potential detriments to long-term health (particularly cardiovascular health) is hotly debated. Unfortunately, that debate has largely focused on whether all patients or no patients at all should be treated with RT. The RAPID trial was one of the first to evaluate the omission of radiation therapy based on a negative PET after chemotherapy. After 3 cycles of ABVD and a Deauville 1-2 PET patients were randomized to no further treatment or involved field radiation (IFRT). Those fields encompassed the involved nodal region + 5cm sup/inf and 2cm lateral margins treated with AP/PA fields. Gulp. Three-year PFS was 94.6% with IFRT vs 90.8% without, and it was 97.1% vs 90.8% for those treated per protocol. ]Using individual patient anthracycline dose and cardiovascular radiation dose from treatment plans, this study estimated the 30-year risk of cardiovascular disease (CVD) and CVD mortality, which were compared to baseline CVD risk for the UK population. As you might imagine, CV dose varied widely and was negligible for those with disease outside the neck or mediastinum. Over half of patients had a mean heart dose < 1 Gy and ⅔ had a MHD < 5 Gy. For the entire cohort, the average 30-year risk of CVD mortality was 5.02%, which was composed of baseline risk (3.52%), anthracycline risk (0.94% excess risk), and IFRT risk (0.56%). Just as CV dose varied widely, excess CVD mortality risk from IFRT ranged from 0.01% to 6.79%. Two-thirds of patients had < 0.5% excess CVD mortality risk at 30 years from IFRT. And of note, nearly ⅔ of patients actually had a higher excess CVD mortality risk from anthracyclines than from IFRT. The point is that a majority of HL patients could derive disease benefit from radiation with minimal increase in excess cardiovascular risk.

TBL: Among patients treated with radiation for early stage HL, “the magnitude of [CVD mortality] risk varies widely and, for a majority of patients, the benefit of reduced HL relapse substantially outweighs the risk of CVD.”  | Cutter, J Clin Oncol 2021

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