No increased risk of mature B-cell non-Hodgkin lymphoma after Q fever detected: results from a 16-year ecological analysis of the Dutch population incorporating the 2007-2010 Q fever outbreak.

BACKGROUND: A causative role of Coxiella burnetii (the causative agent of Q fever) in the pathogenesis of B-cell non-Hodgkin lymphoma (NHL) has been suggested, although supporting studies show conflicting evidence. We assessed whether this association is present by performing a detailed analysis on the risk of mature B-cell NHL after Q fever during and after the largest Q fever outbreak reported worldwide in the entire Dutch population over a 16-year period. METHODS: We performed an ecological analysis. The incidence of mature B-cell NHL in the entire Dutch population from 2002 until 2017 was studied and modelled with reported acute Q fever cases as the determinant. The adjusted relative risk of NHL after acute Q fever as the primary outcome measure was calculated using a Poisson regression. RESULTS: Between January 2002 and December 2017, 266 050 745 person-years were observed, with 61 424 diagnosed with mature B-cell NHL. In total, 4310 persons were diagnosed with acute Q fever, with the highest incidence in 2009. The adjusted relative risk of NHL after acute Q fever was 1.02 (95% CI 0.97-1.06, P = 0.49) and 0.98 (95% CI 0.89-1.07, P = 0.60), 0.99 (95% CI 0.87-1.12, P = 0.85) and 0.98 (95% 0.88-1.08, P = 0.67) for subgroups of diffuse large B-cell lymphoma, follicular lymphoma or B-cell chronic lymphocytic leukaemia, respectively. Modelling with lag times (1-4 years) did not change interpretation. CONCLUSION: We found no evidence for an association between C. burnetii and NHL after studying the risk of mature B-cell NHL after a large Q fever outbreak in Netherlands.

Characterization of Oligometastatic Disease in a Real-World Nationwide Cohort of 3447 Patients With de Novo Metastatic Breast Cancer.

Background: Observational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC. Methods: 3535 patients aged younger than 80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting, the analysis cohort (n = 3447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox regression models with inverse-sampling-probability weighting to study associations with OS and progression-free survival in OMBC. All statistical tests were 2-sided. Results: Compared with more than 5 distant metastases, adjusted hazard ratios for OS (with 95% confidence interval [CI] based on robust standard errors) for 1, 2-3, and 4-5 metastases were 0.70 (95% CI = 0.52 to 0.96), 0.63 (95% CI = 0.45 to 0.89), and 0.91 (95% CI = 0.61 to 1.37), respectively. Ten-year OS estimates for patients with no more than 3 vs more than 3 metastases were 14.9% and 3.4% (P < .001). In multivariable analyses, premenopausal andperimenopausal status, absence of lung metastases, and local therapy of metastases (surgery and/or radiotherapy) added to systemic therapy were statistically significantly associated with better OS and progression-free survival in OMBC, independent of local therapy of the primary tumor. Conclusion: OMBC defined as MBC limited to 1-3 metastases was associated with favorable OS. In OMBC, local therapy of metastases was associated with better OS, particularly if patients were premenopausal or perimenopausal without lung metastases.

Ascertainment of cancer in longitudinal research: The concordance between the Rotterdam Study and the Netherlands Cancer Registry.

Complete and accurate registration of cancer is needed to provide reliable data on cancer incidence and to investigate aetiology. Such data can be derived from national cancer registries, but also from large population-based cohort studies. Yet, the concordance and discordance between these two data sources remain unknown. We evaluated completeness and accuracy of cancer registration by studying the concordance between the population-based Rotterdam Study (RS) and the Netherlands Cancer Registry (NCR) between 1989 and 2012 using the independent case ascertainment method. We compared all incident cancers in participants of the RS (aged ≥45 years) to registered cancers in the NCR in the same persons based on the date of diagnosis and the International Classification of Diseases (ICD) code. In total, 2,977 unique incident cancers among 2,685 persons were registered. Two hundred eighty-eight cancers (9.7%) were coded by the RS that were not present in the NCR. These were mostly nonpathology-confirmed lung and haematological cancers. Furthermore, 116 cancers were coded by the NCR, but not by the RS (3.9%), of which 20.7% were breast cancers. Regarding pathology-confirmed cancer diagnoses, completeness was >95% in both registries. Eighty per cent of the cancers registered in both registries were coded with the same date of diagnosis and ICD code. Of the remaining cancers, 344 (14.5%) were misclassified with regard to date of diagnosis and 72 (3.0%) with regard to ICD code. Our findings indicate that multiple sources on cancer are complementary and should be combined to ensure reliable data on cancer incidence.

Exposure to Coxiella burnetii and risk of non-Hodgkin lymphoma: a retrospective population-based analysis in the Netherlands.

BACKGROUND: An association between Coxiella burnetii and non-Hodgkin lymphoma has been suggested. After a large Q fever epidemic in the Netherlands (2007-10), we postulated that the incidence of non-Hodgkin lymphoma would be increased during and after the epidemic in areas with a high endemicity of Q fever compared with those with low endemicity. METHODS: We did a retrospective population-based analysis and calculated relative risks (RRs) of non-Hodgkin lymphoma during 1-year periods before, during, and after the Q fever epidemic, for areas with intermediate and high endemicity of Q fever compared with low endemic areas. We also calculated the RR of non-Hodgkin lymphoma in people with chronic Q fever compared with the general population. FINDINGS: Between Jan 1, 2002, and Dec 31, 2013, 48 760 cases of non-Hodgkin lymphoma were diagnosed. The incidence of non-Hodgkin lymphoma ranged from 21·4 per 100 000 per year in 2002 to 26·7 per 100 000 per year in 2010. A significant association with non-Hodgkin lymphoma was noted in 2009 for areas with a high endemicity of Q fever compared with low endemic areas (RR 1·16, 95% CI 1·02-1·33; p=0·029); no further associations were noted in any other year or for areas with intermediate Q fever endemicity. Among 439 individuals with chronic Q fever, five developed non-Hodgkin lymphoma, yielding a crude absolute risk of 301·0 cases per 100 000 per year (RR 4·99, 95% CI 2·07-11·98; p=0·0003) compared with the general population in the Netherlands. INTERPRETATION: These findings do not support the hypothesis that Q fever has a relevant causal role in the development of non-Hodgkin lymphoma. Several limitations, inherent to the design of this study, might lead to both underestimation and overestimation of the studied association. FUNDING: Foundation Q-support and Institut Mérieux.