{"entity":{"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","aka":["Schaapveld 2015","Dutch Hodgkin late-effects cohort","Second malignancy after Hodgkin lymphoma"],"tldr":"Of nearly 4,000 Dutch people cured of Hodgkin lymphoma, almost half developed another cancer within forty years, and the gentler treatments introduced in the late 1980s had not reduced that risk.","summary":"This is the cohort that defines the cost of curing Hodgkin lymphoma. 3,905 people in the Netherlands who had survived at least five years after starting treatment between 1965 and 2000, aged 15 to 50 at the time, were followed and compared with cancer incidence in the general population.\n\nAt a median follow-up of 19.1 years, 1,055 second cancers were diagnosed in 908 patients, a standardised incidence ratio of 4.6 (95 per cent confidence interval 4.3 to 4.9). The risk was still raised 35 years or more after treatment (3.9, 2.8 to 5.4), and the cumulative incidence of a second cancer at 40 years was 48.5 per cent (45.4 to 51.5).\n\nThe finding that mattered most was the one the authors did not expect. The cumulative incidence of second solid cancers did not differ between the 1965 to 1976, 1977 to 1988 and 1989 to 2000 treatment periods (p = 0.71 for heterogeneity), despite the less toxic protocols introduced in the late 1980s. Breast cancer risk was lower in patients treated with supradiaphragmatic radiotherapy that spared the axilla than with mantle-field irradiation (hazard ratio 0.37, 0.19 to 0.72), but not lower in the most recent period. A cumulative procarbazine dose of 4.3 grams per square metre or more, which is associated with premature menopause, was associated with lower breast cancer risk (hazard ratio 0.57, 0.39 to 0.84) and higher gastrointestinal cancer risk (2.70, 1.69 to 4.30).","asOf":"2026-10-01","links":[{"label":"New England Journal of Medicine 2015","url":"https://doi.org/10.1056/NEJMoa1505949"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26699166/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/26699166"}],"tags":["lymphoma-evidence"],"related":["paper-van-nimwegen-cardiovascular-disease-after-hodgkin-jama-intern-med-2015","paper-travis-breast-cancer-after-hodgkin-radiotherapy-jama-2003","lymphoma-roadmap"],"cancers":["hodgkin-lymphoma","early-stage-classical-hodgkin-lymphoma","advanced-stage-classical-hodgkin-lymphoma"],"sections":["radiation","supportive-care","prevention"],"technologies":["radiotherapy","proton-therapy"],"targets":[],"drugs":["procarbazine"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["hd10","hd16","radar-hodgkin"],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol","b-overdiagnosis"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1505949","pmid":"26699166","authors":"Schaapveld M, Aleman BM, van Eggermond AM, et al.","paperType":"observational","findings":["Among 3,905 five-year survivors of Hodgkin lymphoma, 1,055 second cancers occurred in 908 patients, a standardised incidence ratio of 4.6 (95 per cent confidence interval 4.3 to 4.9) against the general population.","The cumulative incidence of a second cancer at 40 years was 48.5 per cent (45.4 to 51.5).","Risk remained raised 35 years or more after treatment, with a standardised incidence ratio of 3.9 (2.8 to 5.4).","The cumulative incidence of second solid cancers did not differ between the 1965 to 1976, 1977 to 1988 and 1989 to 2000 treatment periods (p = 0.71 for heterogeneity).","A cumulative procarbazine dose of 4.3 grams per square metre or more was associated with lower breast cancer risk (hazard ratio 0.57, 0.39 to 0.84) and higher gastrointestinal cancer risk (2.70, 1.69 to 4.30)."],"whatItMeans":"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.","caveats":["Patients treated up to 2000, so the cohort does not include modern involved-site radiotherapy fields, proton therapy, or the brentuximab and checkpoint inhibitor regimens; the risks for people treated today are unknown and may be lower.","An observational cohort compared with population rates, not a randomised comparison of treatment eras.","The absence of a difference between treatment periods may partly reflect insufficient follow-up in the most recent group.","Dutch population rates may not transfer to populations with different background cancer incidence."],"changedPractice":true,"participants":3905},"route":"/key-papers/paper-schaapveld-second-cancer-risk-40-years-hodgkin-nejm-2015/","neighbours":{"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-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019","kind":"paper","name":"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","route":"/key-papers/paper-ghsg-hd16-pet-guided-early-favourable-hodgkin-jco-2019/"}],"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":"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/"}],"section":[{"id":"prevention","kind":"section","name":"Prevention & Risk","route":"/fronts/prevention/"},{"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":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"drug":[{"id":"procarbazine","kind":"drug","name":"Procarbazine","route":"/drugs/procarbazine/"}],"trial":[{"id":"hd10","kind":"trial","name":"GHSG HD10","route":"/trials/hd10/"},{"id":"hd16","kind":"trial","name":"GHSG HD16","route":"/trials/hd16/"},{"id":"radar-hodgkin","kind":"trial","name":"RADAR","route":"/trials/radar-hodgkin/"}],"bottleneck":[{"id":"b-overdiagnosis","kind":"bottleneck","name":"Overdiagnosis and false alarms","route":"/bottlenecks/b-overdiagnosis/"},{"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/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"lymphoma-ev-radiotherapy-free-early-hodgkin","kind":"idea","name":"A radiotherapy-free cure for early Hodgkin lymphoma that actually holds","route":"/ideas/lymphoma-ev-radiotherapy-free-early-hodgkin/"},{"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","route":"/ideas/lymphoma-ev-late-effects-of-the-treatments-given-now/"}]}}