{"entity":{"id":"lymphoma-ev-late-effects-of-the-treatments-given-now","kind":"idea","name":"Measure the late effects of the treatments being given now, not the ones given in 1975","aka":["Modern Hodgkin survivorship cohorts","Late effects of brentuximab, checkpoint inhibitors and CAR-T"],"tldr":"Everything known about the long-term cost of curing lymphoma comes from people treated decades ago with much larger radiation fields. Nobody knows the forty-year risks of what is given today.","summary":"The immune treatments make this more urgent, not less. Checkpoint inhibitors cause endocrine and autoimmune effects whose 20-year course is unknown; CAR-T carries prolonged cytopenias, hypogammaglobulinaemia and a second-malignancy signal that regulators have asked about; brentuximab vedotin causes peripheral neuropathy that can persist. The field is making de-escalation decisions on a harm estimate drawn from a treatment nobody gives any more.","asOf":"2026-10-01","links":[],"tags":["lymphoma-evidence"],"related":["lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":["supportive-care","radiation"],"technologies":["radiotherapy","imrt-igrt","proton-therapy","car-t","checkpoint-inhibitor"],"targets":[],"drugs":["brentuximab-vedotin","nivolumab","pembrolizumab","axicabtagene-ciloleucel","doxorubicin","procarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-real-world-evidence","b-data-silos"],"keyPapers":["paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Prospective survivorship cohorts of patients treated with modern involved-site radiotherapy, brentuximab vedotin, checkpoint inhibitors and CAR-T will show a different late-effect profile from the historical cohorts, and knowing it will change how much de-escalation is worth pursuing.","rationale":"The Dutch cohorts, which set the terms of every Hodgkin de-escalation debate, enrolled patients treated between 1965 and 2000 with mantle fields; Travis measured breast cancer risk against doses up to and beyond 40 Gy. Modern involved-site radiotherapy delivers 20 Gy to a small volume, and the chemotherapy has changed completely. Schaapveld's most important finding is that second solid cancer incidence did not fall between the 1965 to 1976 and 1989 to 2000 treatment periods, which could mean that de-escalation so far has not helped, or that follow-up in the recent group is too short to tell. Only a cohort can distinguish those.","test":"Enrol consecutive patients treated for Hodgkin lymphoma and aggressive B-cell lymphoma from a defined date into a prospective cohort with linkage to cancer registries, cardiovascular records and fertility outcomes, with sufficient radiotherapy dosimetry and cumulative drug dose captured to support dose-response analysis at 10, 20 and 30 years. Report the first comparison against the historical cohorts at 15 years rather than waiting for 40.","maturity":"speculative","actor":"research","cost":"medium","horizonYears":15},"route":"/ideas/lymphoma-ev-late-effects-of-the-treatments-given-now/","neighbours":{"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"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","route":"/roadmaps/lymphoma-roadmap/"}],"cancer":[{"id":"advanced-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Advanced-stage classical Hodgkin lymphoma (stage III to IV)","route":"/cancers/advanced-stage-classical-hodgkin-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"early-stage-classical-hodgkin-lymphoma","kind":"cancer","name":"Early-stage classical Hodgkin lymphoma (stage I to II)","route":"/cancers/early-stage-classical-hodgkin-lymphoma/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"section":[{"id":"radiation","kind":"section","name":"Radiation Therapy","route":"/fronts/radiation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"term":[{"id":"radiotherapy","kind":"term","name":"Radiotherapy","route":"/terms/radiotherapy/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"brentuximab-vedotin","kind":"drug","name":"Brentuximab vedotin","route":"/drugs/brentuximab-vedotin/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"procarbazine","kind":"drug","name":"Procarbazine","route":"/drugs/procarbazine/"}],"bottleneck":[{"id":"b-data-silos","kind":"bottleneck","name":"Data silos","route":"/bottlenecks/b-data-silos/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-real-world-evidence","kind":"bottleneck","name":"Weak real-world evidence and registries","route":"/bottlenecks/b-real-world-evidence/"}],"paper":[{"id":"paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003","kind":"paper","name":"Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease","route":"/key-papers/paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003/"},{"id":"paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","kind":"paper","name":"Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk","route":"/key-papers/paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015/"},{"id":"paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015","kind":"paper","name":"Second cancer risk up to 40 years after treatment for Hodgkin's lymphoma","route":"/key-papers/paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015/"}]}}