Role of radiotherapy in refractory/relapsed classical Hodgkin lymphoma in the era of targeted therapies and immunotherapy.
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Relapsed or refractory classical Hodgkin lymphoma (R/R cHL) remains a complex therapeutic challenge despite major advances in systemic treatment. Salvage therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for eligible patients, but contemporary pre-transplant strategies increasingly incorporate brentuximab vedotin (BV) and, more recently, PD-1 inhibitors, which have reshaped the salvage landscape and challenged chemotherapy-only approaches. In this evolving context, radiotherapy (RT) continues to play an important role, although its indications have become more selective and individualized. Available data suggest that RT is particularly relevant for local control of residual disease, limited relapse, or metabolically active lesions, especially in the peri-transplant setting and after novel agents. Peri-transplant RT appears most useful in patients at high risk of locoregional relapse, including those with bulky disease, primary refractory lymphoma, residual PET positivity, or incomplete response before ASCT. By contrast, evidence supporting RT after or in combination with novel agents remains limited, largely derived from small, retrospective studies. Data on RT after BV are scarce but suggest excellent local control in carefully selected patients, while the combination of RT and PD-1 blockade appears especially promising, with encouraging efficacy signals from case reports, retrospective series, and recent prospective pediatric/AYA data. Modern RT techniques (IMRT/VMAT, IGRT, DIBH, and involved-site RT) enable response-adapted treatment delivery with improved normal tissue sparing. Overall, RT remains a valuable component of salvage strategies in R/R cHL in the era of BV and PD-1 inhibitors, but prospective studies are needed to better define patient selection, sequencing, target volumes, and dose prescriptions.