Survival and treatment related toxicity in classical Hodgkin lymphoma

Treating early-stage classical Hodgkin lymphoma (cHL) by adding radiotherapy to chemotherapy gives better disease control compared to chemotherapy only. With a low median age at diagnosis, the risk from cHL needs to be weighed against the risk of treatment toxicity. Historical reports indicate substantial toxicity from radiotherapy, with excess morbidity and mortality. These results are based on radiotherapy techniques no longer in use. Modern radiotherapy might not cause the same level of long-term risks. By linking lymphoma registers and health registers, the present thesis analyses results for two cohorts of patients treated for early-stage cHL with combined modality. The cohorts are population-based and have been treated with radiation fields that are reduced compared with fields used in earlier population-based cohorts. The cohorts exhibit excess morbidity, hazard ratio (HR) 1.6 (95% Confidence Interval, CI, 1.1–2.4) for second cancers, HR 1.4 (95%CI, 1.1–1.8) for diseases of the circulatory system, and HR 2.6 (95%CI, 1.6–4.3) for diseases of the respiratory system. The first cohort, diagnosed 1999–2005, does not deviate from expected survival in the general population. The only subgroup analysed with excess mortality consists of patients with progressive cHL within 5 years of follow-up. The later cohort, patients diagnosed 2006–2015, exhibits a small but statistically significant excess mortality, relative survival rate 0.97 (95%CI, 0.95–0.99) at 10 years of follow-up. In analyses of years of life lost according to cause of death, second malignancies are the leading cause of death, 1.17 years/patient compared with 0.41 years/comparator (p=0.004) in the first cohort. Progressive cHL is the dominating cause of death in the second cohort. In these two cohorts with early-stage cHL treated with combined modality, excess morbidity exists, but on a much lower level than in previously published population-based cohorts, which reported standardised incidence ratios of 4–5 for second cancers and 4–7 for cardiovascular disease. Survival is excellent with only marginal or no excess mortality compared with the general population. The excess mortality in the second cohort is almost certainly caused by deaths due to progressive cHL. In conclusion, the substantial reduction in excess morbidity from treatment toxicity result in no, or minimal excess mortality. The cause of death that can be correlated to any significant excess mortality is progressive cHL. These results argue in favour of continuing to strive for disease control, suggesting that, at present, combined modality should be used to treat early-stage cHL