Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma:a Swedish population-based study

Considering treatment changes and an improved prognosis of non-Hodgkin lymphoma (NHL) over time, knowledge regarding long-term health outcomes, including late effects of treatment, has become increasingly important. We report on time trends of second primary malignancies (SPMs) in Swedish NHL patients, encompassing the years before as well as after the introduction of anti-CD20 antibody therapy. We identified NHL patients in the Swedish Cancer Register 1993 to 2014 and matched comparators from the Swedish Total Population Register. The matched cohort was followed through 2017. By linking to the Swedish Lymphoma Register, subcohort analyses by NHL subtype were performed. Flexible parametric survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of SPM among patients and comparators. Among 32 100 NHL patients, 3619 solid tumors and 217 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) cases were observed, corresponding to a 40% higher rate of solid tumors (HR(solid tumors) = 1.4; 95% CI, 1.4-1.5) and a 5-fold higher rate of MDS/AML (HR(MDS/AML )= 5.2; 95% CI, 4.4-6.2) than for comparators. Overall, the observed excess risks for solid tumors or MDS/AML remained stable over the study period, except for follicular lymphoma, where the excess rate of MDS/AML attenuated with time (P for trend = .012). We conclude that NHL survivors have an increased risk of both solid tumors and hematologic malignancies, in particular MDS/AML. Stable excess risks over time indicate that contemporary treatment standards are not associated with modified SPM risk. Encouragingly, decreasing rates of MDS/AML were noted among patients with follicular lymphoma, possibly due to the increasing use of nonchemotherapy-based treatments

Aspirin intake and breast cancer survival – a nation-wide study using prospectively recorded data in Sweden

Background: Aspirin (ASA) use has been associated with improved breast cancer survival in several prospective studies. Methods: We conducted a nested case–control study of ASA use after a breast cancer diagnosis among women using Swedish National Registries. We assessed prospectively recorded ASA exposure during several different time windows following cancer diagnosis using conditional logistic regression with breast cancer death as the main outcome. Within each six-month period of follow-up, we categorized dispensed ASA doses into three groups: 0, less than 1, and 1 or more daily doses. Results: We included 27,426 women diagnosed with breast cancer between 2005 and 2009; 1,661 died of breast cancer when followed until Dec 31, 2010. There was no association between ASA use and breast cancer death when exposure was assessed either shortly after diagnosis, or 3–12 months before the end of follow-up. Only during the period 0–6 months before the end of follow-up was ASA use at least daily compared with non-use associated with a decreased risk of breast cancer death: HR (95% CI) = 0.69 (0.56-0.86). However, in the same time-frame, those using ASA less than daily had an increased risk of breast cancer death: HR (95% CI) = 1.43 (1.09-1.87). Conclusions: Contrary to other studies, we did not find that ASA use was associated with a lower risk of death from breast cancer, except when assessed short term with no delay to death/end of follow-up, which may reflect discontinuation of ASA during terminal illness

Risk of diabetes and the impact on preexisting diabetes in patients with lymphoma treated with steroid-containing immunochemotherapy

First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD

Anaplastic large cell lymphoma, ALK-negative

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Ultraviolet light, autoimmune disorders and the etiology of malignant lymphomas

Malignant lymphomas constitute a clinically and morphologically diverse group of malignancies that may also differ etiologically. The incidence of the most common non-Hodgkin lymphomas (NHL) has increased dramatically worldwide during the past decades. Established risk factors together only explain a minority of the cases, let alone the NHL increase. Observations of a positive link between skin cancer and NHL have fostered the hypothesis that frequent sun exposure could be a risk factor for both malignancies and a contributing factor to the rise in NHL incidence. The aim of this thesis was to test the hypothesis of a positive association between sun exposure and malignant lymphomas, and to evaluate the role of autoimmune and chronic inflammatory disorders, especially rheumatoid arthritis (RA) and celiac disease, in the development of malignant lymphoma subtypes, and lymphomagenic mechanisms in this context. We performed a population-based case-control study in all of Denmark and Sweden (the Scandinavian Lymphoma Etiology, or SCALE, study) between 1999 and 2002, including 3,740 patients with malignant lymphomas and 3,187 control subjects aged 18 to 74 years. Based on structured telephone interviews, information was collected on history of ultraviolet (UV) light exposure, sun sensitivity, skin cancer history and other potential risk factors. In contrast with the a priori hypothesis, frequent sun exposure in Denmark/Sweden and abroad and sun burns at different ages were associated with a statistically significant 30-40% reduction in risk of overall NHL, with clear indications of inverse doseresponse trends (all Ptrends, < .003). There was similar but weaker evidence of inverse associations for Hodgkin lymphoma (HL). Self-reported skin cancer history was associated with a doubling in risks of NHL and HL. To test the hypothesis that the established excess risk of lymphomas in RA is due to risk factors shared by both disorders, we undertook a retrospective registry-based cohort study of Swedish patients hospitalized with RA (n=76,527) and the first-degree relatives (n=70,290) of a subset of these patients. Relative risks of malignant lymphomas were assessed by matching the respective cohorts with the population-based cancer register. The RA patients had a doubled risk of malignant lymphomas overall, although the excess risk did not persist beyond 20 years of follow-up. Firstdegree relatives were generally not at increased risk of malignant lymphomas, and thus a prominent role of shared risk factors in RA-related lymphomagenesis was not supported. To evaluate the spectrum of lymphoma subtypes associated with celiac disease, we re-classified 56 malignant lymphoma cases occurring in a large cohort of patients previously hospitalized for celiac disease (n=11,650). Our results indicated that celiac disease patients are at increased risk, not only of the well-described enteropathy-type T-cell lymphoma, but also of non-intestinal T-cell lymphomas and the common B-cell lymphomas compared to the general population. Finally, we estimated relative risks of NHL overall and by subtype in association with several autoimmune and chronic inflammatory disorders, disease phenotype and treatment, using selfreported data in SCALE. We confirmed an increased risk of NHL in RA, systemic lupus erythematosus, primary Sjögren's syndrome and celiac disease, but not in type I diabetes, inflammatory bowel disorders, sarcoidosis or psoriasis. The first four disorders were all specifically associated with diffuse large B-cell lymphoma and with a few more uncommon NHL subtypes. Data suggested a tendency towards higher risks in severe and long-standing inflammation, but there was little to support previous notions of risk associated with medical treatments in these conditions

Stable use of radiotherapy in lymphoma patients over time : A comprehensive national overview of radiotherapy use in Sweden with focus on older patients

Background and purpose The role of radiotherapy (RT) in lymphoma is constantly refined with the advent of novel treatments. However, RT is still an effective treatment and tolerability is high. Therefore, we aimed to describe the use of RT in primary treatment of lymphoma over calendar time, with a specific focus on older patients (age ≥ 70 years) with non-Hodgkin lymphoma (NHL) subtypes. Materials &amp; Methods All adult patients diagnosed with lymphoma from 2007 to 2018 in Sweden were included and followed for survival until end of 2020. Patient characteristics and relative survival (RS) were described for patients with NHL by subtype and RT use. Results In the cohort of lymphoma patients aged ≥ 70 years (n = 12,698) 11 % received RT as part of primary treatment. No decline in use of RT over calendar period was seen. Use of RT as monotherapy was associated with stage I-II disease and older age among patients with stage III-IV disease. Patients with indolent lymphomas aged ≥ 70 years who were selected for treatment with RT as monotherapy with a dose of ≥ 20 Gy had 2-year RS rate of 100 % which remained similar at five years. For patients with DLBCL, RT as monotherapy with a dose of ≥ 20 Gy was mostly administered to patients aged ≥ 85 years with a 2-year RS rate of 68 %. Conclusion The use of RT in first-line lymphoma treatment was stable over calendar time. RT monotherapy is associated with encouraging outcomes among patients with NHL aged ≥ 70 years who were selected to receive this