Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low-dose radiation from natural sources contributes to the risk of childhood ...cancer remains unclear.
In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays.
Children < 16 years of age in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008, and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth.
Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each millisievert increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (95% CI: 1.00, 1.08) for leukemia, 1.01 (95% CI: 0.96, 1.05) for lymphoma, and 1.04 (95% CI: 1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results.
Our study suggests that background radiation may contribute to the risk of cancer in children, including leukemia and CNS tumors.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To assess the cost-effectiveness and budget impact of olaparib as a maintenance therapy in platinum-responsive, metastatic pancreatic cancer patients harboring a germline BRCA1/2 mutation, using the ...Swiss context as a model.
Based on data from the POLO trial, published literature and local cost data, we developed a partitioned survival model of olaparib maintenance including full costs for BRCA1/2 germline testing compared to FOLFIRI maintenance chemotherapy and watch-and-wait. We calculated the incremental cost-effectiveness ratio (ICER) for the base case and several scenario analyses and estimated 5-year budget impact.
Comparing olaparib with watch-and wait and maintenance chemotherapy resulted in incremental cost-effectiveness ratios of CHF 2,711,716 and CHF 2,217,083 per QALY gained, respectively. The 5-year costs for the olaparib strategy in Switzerland would be CHF 22.4 million, of which CHF 11.4 million would be accounted for by germline BRCA1/2 screening of the potentially eligible population. This would amount to a budget impact of CHF 15.4 million (USD 16.9 million) versus watch-and-wait.
Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Assessing exposure to infections in early childhood is of interest in many epidemiological investigations. Because exposure to infections is difficult to measure directly, epidemiological studies ...have used surrogate measures available from routine data such as birth order and population density. However, the association between population density and exposure to infections is unclear. We assessed whether neighbourhood child population density is associated with respiratory infections in infants.
With the Basel-Bern lung infant development study (BILD), a prospective Swiss cohort study of healthy neonates, respiratory symptoms and infections were assessed by weekly telephone interviews with the mother throughout the first year of life. Using population census data, we calculated neighbourhood child density as the number of children < 16 years of age living within a 250 m radius around the residence of each child. We used negative binomial regression models to assess associations between neighbourhood child density and the number of weeks with respiratory infections and adjusted for potential confounders including the number of older siblings, day-care attendance and duration of breastfeeding. We investigated possible interactions between neighbourhood child population density and older siblings assuming that older siblings mix with other children in the neighbourhood.
The analyses included 487 infants. We found no evidence of an association between quintiles of neighbourhood child density and number of respiratory symptoms (p = 0.59, incidence rate ratios comparing highest to lowest quintile: 1.15, 95%-confidence interval: 0.90-1.47). There was no evidence of interaction with older siblings (p = 0.44). Results were similar in crude and in fully adjusted models.
Our study suggests that in Switzerland neighbourhood child density is a poor proxy for exposure to infections in infancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Space–time clustering of childhood cancers Kreis, Christian; Doessegger, Eliane; Lupatsch, Judith E. ...
European journal of epidemiology,
01/2019, Letnik:
34, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The aetiology of childhood cancers remains largely unknown. Space–time clustering of cases might imply an aetiological role of infections. We aimed to review the evidence of space–time clustering of ...specific childhood cancers. We searched Medline and Embase for population-based studies that covered a pre-defined study area, included cases under 20 years of age and were published before July 2016. We extracted all space–time clustering tests and calculated the proportion of positive tests per diagnostic group. In a pooled analysis, we performed a Knox test of the number of pairs of cases close to each other in time and space pooled across studies. 70 studies met our eligibility criteria, 32 of which reported Knox tests. For leukaemia, the proportion of positive tests was higher than expected by chance at both time of diagnosis (26%) and birth (11%). The pooled analysis showed strong evidence of clustering at diagnosis for children aged 0–5 years for a spatial and temporal lag of 5 km and 6 months, respectively (p < 0.001). The evidence was mixed for lymphoma and tumours of the central nervous system. The current study suggests that leukaemia cases cluster in space–time due to an aetiological factor affecting children under 5 years of age. The observed pattern of clustering of young children close to time of diagnosis is compatible with Greaves’ delayed-infections-hypothesis.
Purpose
Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to ...investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth.
Methods
We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0–15 and 0–4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Results
The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12–1.69) and multiple birth (1.89, 1.24–2.86). These associations were similar for ALL and stronger for leukemia at ages 0–4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43–22.03 for fourth or later born children). We found no associations with other perinatal characteristics.
Conclusion
This register-based case–control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.
Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL ...around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters.
We identified cases of persons born and diagnosed between 1985 and 2014 at age 0-15 years from the Swiss Childhood Cancer Registry. We determined spatial and temporal lags that maximized evidence of clustering based on the Knox test and classified cases born within these lags from another case as clustered. Using logistic regression adjusted for child population density, we determined whether clustering status was associated with age at diagnosis, immunophenotype, cytogenetic subtype, perinatal and socioeconomic characteristics, and pollution sources.
Analyses included 1,282 cases of which 242 were clustered (born within 1 km and 2 years from another case). Of all investigated characteristics only the t(12;21)(p13;q22) translocation (resulting in ETV6-RUNX1 fusion) differed significantly in prevalence between clustered and nonclustered cases (40% and 25%, respectively; adjusted OR 2.54 1.52-4.23; p = 0.003). Spatio-temporal clustering was driven by an excess of aggregations of two or three children rather than by a few large clusters.
Our findings suggest ETV6-RUNX1 is associated with space-time clustering of CL and are consistent with an infection interacting with that oncogene in early life leading to clinical leukemia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive ...prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland.
To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature.
The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events.
This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.
•Consolidative local therapy in oligometastatic NSCLC can be cost-effective.•Local therapy costs and quality of life were the most important drivers.•Ongoing studies in oligometastatic disease should ...include cost-effectiveness.
Novel systemic therapies have improved the prognosis of metastatic non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter of ongoing debate. More recently, local therapies (LT) such as radiotherapy and surgery have been suggested as additional treatment in oligometastatic NSCLC demonstrating an improved progression-free survival (PFS) in a phase II trial compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to assess the cost-effectiveness of local therapies in oligometastatic NSCLC.
We constructed a Markov model comparing the cost-effectiveness of LT versus MC for oligometastatic NSCLC from the Swiss healthcare payer’s perspective. Treatment specifications and PFS were based on the phase II trial (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial. Utilities were taken from published data. Primary outcome was the incremental cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted life-year (QALY) gained).
PFS in the model was 3.8 months for MC and 11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24 QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7% of the simulations.
LT may be cost-effective for selected patients with oligometastatic NSCLC responding to first-line systemic therapy.
Regular follow-up care is essential for childhood cancer survivors, but we know little about physicians' experience with it. We aimed to describe: (1) involvement of Swiss physicians in follow-up ...care; (2) content of follow-up care provided; (3) problems encountered; and (4) additional resources needed.
Within this cross-sectional survey we sent adapted questionnaires via professional associations to a sample of medical oncologists (MOs), paediatric oncologists (POs), general practitioners (GPs) and paediatricians (P) in Switzerland. Only oncologists involved in follow-up care were asked to report problems. GPs and Ps not involved in follow-up could indicate why. All physicians were asked about the content of follow-up care provided and additional resources needed.
A total of 183 physicians responded (27 MO, 13 PO, 122 GP, 21 P). Involved in follow-up were 81% of MOs, 85% of POs, 39% of GPs and 81% of Ps. Follow-up content differed between oncologists (MO and PO) and generalists (GP and P), with generalists examining or informing less in regard to the former cancer. POs reported more problems than MOs: many POs reported problems with transition of survivors to adult care (91%), and because of financial resources (73%) and time restraints (73%). MOs reported most problems during transition (23%). Not being aware of a survivor was the most common reason for GPs and Ps not participating in follow-up (74%). All groups reported a need for standardised protocols (85-91%) and specialised training (55-73%). GPs (94%) and Ps (100%) additionally desired more support from oncologists.
To improve quality and efficiency of follow-up care a national follow-up care model including standardised protocols and guidelines needs to be developed.
•We pooled data from two French case-control studies (469 cases and 2719 controls).•Farm visits and contact with pets in early life were inversely associated with childhood brain tumours ...(CBT).•Day-care in early life was not associated with CBT.•A history of common infections or atopic conditions were not associated with CBT.
Few studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals.
We pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders.
The analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7–1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7–1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56–1.1). Farm visits (OR: 0.6, 95%CI: 0.5–0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6–1.0) in the first year of life were inversely associated with CBT.
Our findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation.
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