Temporal trends in treatment‐related incidence of diseases of the circulatory system among Hodgkin lymphoma patients

Abstract

While Hodgkin lymphoma (HL) survival has improved, treatment‐related complications remain a concern. As a measure of treatment‐related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18–80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model‐based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow‐up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009–2013 vs. 1985–1988: EIRR = 0.63, 95% CI: 0.42–0.95). The 5‐ and 10‐year excess incidence of DCS decreased between 1985 and 1994 for 25‐year‐olds (5‐year‐EIRR1994 = 0.32, 95% CI: 0.12–0.92) and 60‐year‐olds (5‐year‐EIRR1994 = 0.45, 95% CI: 0.24–0.88), but remained stable thereafter. No improvements were observed among 75‐year‐olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment‐related incidence of DCS has declined since the mid‐1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies.

A multistate model incorporating estimation of excess hazards and multiple time scales

“…Still, the risk of being diagnosed with excess DCS persists in the new millennium among HL patients in Sweden. 11 Although a reduction in excess DCS mortality does not necessarily imply a reduction in excess incidence, it remains difficult to draw conclusions on the relationship between HL and its treatment and risk of DCS together with fatality of DCS. By incorporating morbidity and mortality in the same setting, and separating between the incidence attributable to the cancer and that expected in the absence of cancer, we have illustrated one way to overcome this issue.…”

“…This cohort has been described in detail previously. 11 Patients were followed until death, emigration, or end of study period (31st of December, 2014), whichever came first. Incident cases of DCS were linked to the HL patients using the Swedish Inpatient Register.…”

“…However, the same approach can be used to estimate excess incidence rates. 11 As such, the excess incidence of some disease of interest can be interpreted as the portion of incidence attributable to the underlying cancer and its treatment, given that the expected rates are appropriate for the population diagnosed with cancer.…”

“…14 Further extensions of these methods have been applied to study excess DCS incidence in HL patients. 11 In the latter article, the expected incidence rate was modeled using a constant rate model with two time scales (calendar year and age) with two-way interactions. In the mentioned articles, the cumulative probabilities were calculated using numerical integration, in the presence of competing risks.…”

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

“…National guidelines for cHL in Norway and Sweden recommend surveillance programmes for late toxicity, but such recommendations have not been present during the entire study period. Excess mortality and morbidity due to cardiovascular disease has also decreased in HL survivors in Sweden since the mid‐1980s (Eloranta et al , ; Weibull et al , ). Furthermore, the decreasing proportion of smokers in the population (Ng et al , ) may contribute to the reduced incidence of late fatal complications.…”