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

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

Cost-effectiveness of internet-based cognitive-behavioural therapy and physical exercise for depression

Background Both internet-based cognitive-behavioural therapy (ICBT) and physical exercise are alternatives to treatment as usual (TAU) in managing mild to moderate depression in primary care.Aims To determine the cost-effectiveness of ICBT and physical exercise compared with TAU in primary care.Method Economic evaluation of a randomised controlled trial (N = 945) in Sweden. Costs were estimated by a service use questionnaire and used together with the effects on quality-adjusted life-years (QALYs). The primary 3-month healthcare provider perspective in primary care was complemented by a 1-year societal perspective.Results The primary analysis showed that incremental cost per QALY gain was €8817 for ICBT and €14 571 for physical exercise compared with TAU. At the established willingness-to-pay threshold of €21 536 (£20 000) per QALY, the probability of ICBT being cost-effective is 90%, and for physical exercise is 76%, compared with TAU.Conclusions From a primary care perspective, both ICBT and physical exercise for depression are likely to be cost-effective compared with TAU.Declaration of interest None

Limited, But Not Eliminated, Excess Long-Term Morbidity in Stage I-IIA Hodgkin Lymphoma Treated With Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Limited-Field Radiotherapy

PURPOSE Balancing disease control and toxicity from chemotherapy and radiotherapy (RT) when treating early-stage classical Hodgkin lymphoma (cHL) is important. Available data on long-term toxicity after RT for cHL mostly refer to RT techniques no longer in use. We aimed to describe long-term toxicity from modern limited-field (LF)-RT after two or four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). PATIENTS AND METHODS This study included all patients with cHL treated with two or four cycles of ABVD and 30 Gy LF-RT during 1999-2005 in Sweden. Patients (n = 215) and comparators (n = 860), matched for age, gender, and region of residence, were cross-checked against national health registries for malignancies, diseases of the circulatory system (DCS), and diseases of the respiratory system (DRS) from the day of diagnosis of cHL. RESULTS The risk of a malignancy was higher for patients than comparators, hazard ratio (HR) 1.5 (95% CI, 1.0 to 2.4), as was the risk for DCS 1.5 (95% CI, 1.1 to 2.0) and for DRS 2.6 (95% CI, 1.6 to 4.3). The median followup was 16 years (range, 12-19 years). Of individual diagnoses in DCS, only venous thromboembolism was statistically significantly elevated. If the first 6 months (ie, time of active treatment for cHL) were excluded and censoring at relapse of cHL or diagnosis of any malignancy, the increased HR for venous thromboembolism diminished. Most of the excess risk for DRS consisted of asthma, HR 3.5 (95% CI, 1.8 to 6.8). Patients diagnosed with DRS were significantly younger than comparators. CONCLUSION Compared with toxicity from earlier RT techniques, excess morbidity was not eliminated, but lower than previously reported. The elevated risk of DRS was driven by diagnosis of asthma, which could in part be explained by misdiagnosis of persisting pulmonary toxicity.Funding Agencies|Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond; Swedish Cancer Society</p

Real‐world data on treatment concepts in classical Hodgkin lymphoma in Sweden 2000–2014, focusing on patients aged >60 years

Abstract Treatment for patients > 60 years with classical Hodgkin lymphoma (cHL) is problematic; there is no gold standard, and outcome is poor. Using the Swedish Lymphoma Registry, we analysed all Swedish patients diagnosed with cHL between 2000 and 2014 (N = 2345; median age 42 years; 691 patients were >60 years). The median follow‐up time was 6.7 years. Treatment for elderly patients consisted mainly of ABVD or CHOP, and the younger patients were treated with ABVD or BEACOPP (with no survival difference). In multivariable analysis of patients > 60 years, ABVD correlated with better survival than CHOP (p = 0.027), and ABVD became more common over time among patients aged 61–70 years (p = 0.0206). Coinciding with the implementation of FDG‐PET/CT, the fraction of advanced‐stage disease increased in later calendar periods, also in the older patient group. Survival has improved in cHL patients > 60 years (p = 0.027), for whom ABVD seems superior to CHOP

No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy

When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality