Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019.

The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59-1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62-1.77), for male individuals (SIR, 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SIR, 1.92; 95% CI, 1.79-2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96-2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53-1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

Stage-specific trends in primary therapy and survival in follicular lymphoma: a nationwide population-based analysis in the Netherlands, 1989-2016.

We assessed stage-specific trends in primary therapy and relative survival among adult follicular lymphoma (FL) patients diagnosed in the Netherlands between 1989-2016 (N = 12,372; median age, 62 years; and 21% stage I disease). Patients were stratified by disease stage and subsequently categorized into four calendar periods (1989-1995, 1996-2002, 2003-2008, and 2009-2016) and three age groups (18-60, 61-70, and >70 years). The use of radiotherapy in stage I FL remained relatively stable over time and across the three age groups (i.e., 66%, 54%, and 49% in 2009-2016, respectively). In stage II-IV FL, the start of chemotherapy within 12 months post-diagnosis decreased over time, indicating a broader application of a watch-and-wait approach. Relative survival improved considerably over time, especially since 2003 when rituximab was introduced in the Netherlands, and for stage III-IV FL patients and older age groups. Five-year relative survival for patients with stage I-II versus stage III-IV FL in the period 2009-2016 was 96% versus 90%, 93% versus 83%, and 92% versus 68% across the three age groups, respectively. Collectively, the improvement in survival since 2003 is accounted for by advances in FL management, particularly the implementation of rituximab. There remains, however, room for improvement among elderly stage III-IV FL patients.

The impact of prior malignancies on the development of second malignancies and survival in follicular lymphoma: A population-based study.

We assessed the impact of a prior malignancy diagnosis (PMD) - as a potential proxy for genetic cancer susceptibility - on the development of a second primary malignancy (SPM) and mortality in follicular lymphoma (FL) patients. From the nationwide Netherlands Cancer Registry, we selected all adult FL patients diagnosed in 1994-2012 (n = 8028) and PMDs and SPMs relative to FL, with follow-up until 2017. We constructed two Fine and Gray models - with death as a competing risk - to assess the association between a PMD and SPM incidence. A PMD was associated with an increased incidence of SPMs (subdistribution hazard ratio [SHR], 1.30; 95% confidence interval [CI], 1.03-1.64) - especially carcinomas of the respiratory tract (SHR, 1.83; 95% CI, 1.10-3.05) and cutaneous squamous cell carcinomas (SHR, 1.58; 95% CI, 1.01-2.45) - and a higher risk of mortality in a multivariable model (HR, 1.43; 95% CI, 1.19-1.71). However, when additionally adjusted for the receipt of systemic therapy and/or radiotherapy before FL diagnosis, only patients who received such therapies had an increased incidence of SPMs (SHR, 1.40; 95% CI, 1.02-1.93). In conclusion, patients with a PMD had a higher rate of SPMs and mortality than those without a PMD, which might have resulted from therapy-related carcinogenesis.