Population-based monitoring of cancer patient survival in situations with imperfect completeness of cancer registration

Selective underascertainment of cases may bias estimates of cancer patient survival. We show that the magnitude of potential bias strongly depends on the time periods affected by underascertainment and on the type of survival analysis (cohort analysis vs period analysis). We outline strategies on how to minimise or overcome potential biases

Occurrence of primary brain tumors in cochlear implant patients in Sweden between 1989 and 2014

Henrik Smeds,1,2 Jeremy Wales,1,2 Tiit Mathiesen,3–6 Mats Talbäck,7 Maria Feychting7 1Department of Otolaryngology, Karolinska University Hospital, Stockholm, Sweden; 2Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; 3Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; 4Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 5Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 6Department of Neurosurgery, Rigshospitalet, Copenhagen, Denmark; 7Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Purpose: Cochlear implants are widely used for hearing rehabilitation of deaf children with congenital deafness or adults with acquired severe-to-profound hearing loss. The sound processor antenna creates a radio frequency-electromagnetic field transmitting the sound signal to the implant, similar to that in a mobile phone. A recent case report suggested a relationship between cochlear implants and malignant glioma, and some epidemiological studies have suggested an increased glioma and acoustic neuroma risk associated with long hours of mobile phone use. An epidemiological study is warranted to evaluate such a relationship in patients with cochlear implants.Patients and methods: To examine whether this chronic radio frequency-electromagnetic field signaling is associated with an increased brain tumor risk, a population-based cohort study was performed examining all 2,748 patients receiving a cochlear implant in Sweden during the years 1989–2014. In all, 3,169 surgeries were performed in the total cohort. The expected occurrence of glioma, meningioma, and acoustic neuroma in the patient cohort was calculated using specific national incidence rates in the Swedish population.Results: Four patients were diagnosed with a brain tumor during follow-up, three of them having meningioma compared with 0.95 expected (standardized incidence ratio =3.16, 95% CI 0.65–9.24), and one had glioma compared with 1.34 expected (standardized incidence ratio =0.75, 95% CI 0.02–4.15). No case of acoustic neuroma was observed compared with 0.09 expected.Conclusion: In this study, we did not find support for concerns raised in a previous case report regarding a potentially higher risk of glioma. The number of brain tumors observed was well within the numbers expected from national incidence figures. Although this was a relatively small cohort with a limited follow-up time, it is the largest epidemiological study to date to address this concern. Keywords: cochlear implants, glioblastoma, neural tumor, non-ionizing radiation, radio frequency-electromagnetic radiatio

Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case–control study

Maral Adel Fahmideh,1 Giorgio Tettamanti,1 Catharina Lavebratt,2 Mats Talbäck,1 Tiit Mathiesen,3,4 Birgitta Lannering,5 Kimberly J Johnson,6,7 Maria Feychting1 1Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4University of Copenhagen, Copenhagen, Denmark; 5Department of Pediatrics, University of Gothenburg, Gothenburg, Sweden; 6Brown School, Washington University in St Louis, St Louis, MO, USA; 7Department of Pediatrics, School of Medicine, Washington University in St Louis, St Louis, MO, USA Purpose: Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring. Patients and methods: The study was a population-based nested case–control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536). Results: Compared with offspring of fathers aged 25–29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35–39 years (odds ratio [OR]=1.43 [95% CI 1.16–1.74]) and ≥40 years (OR =1.74 [95% CI 1.38–2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01–1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age. Conclusion: The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers. Keywords: phacomatoses, nervous system tumor predisposition syndromes, parental age, registry, neurofibromatosi

The effects of twins, parity and age at first birth on cancer risk in Swedish women.

The effect of reproductive history on the risk of cervical, colorectal and thyroid cancers and melanoma has been explored but the results to date are inconsistent. We aimed to examine in a record-linkage cohort study the risk of developing these cancers, as well as breast, ovarian and endometrial cancers, among mothers who had given birth to twins compared with those who had only singleton pregnancies. Women who delivered a baby in Sweden between 1961 and 1996 and who were 15 years or younger in 1961 were selected from the Swedish civil birth register and linked with the Swedish cancer registry. We used Poisson regression to assess associations between reproductive factors and cancer. Twinning was associated with reduced risks of breast, colorectal, ovarian and uterine cancers, although no relative risks were statistically significant. The delivery of twins did not increase the risk of any cancers studied. Increasing numbers of maternities were associated with significantly reduced risks of all tumors except thyroid cancer. We found positive associations between a later age at first birth and breast cancer and melanoma, while there were inverse associations with cervix, ovarian, uterine and colorectal cancers. These findings lend weight to the hypothesis that hormonal factors influence the etiology of colorectal cancer in women, but argue against any strong effect of hormones on the development of melanoma or tumors of the thyroid

Central nervous system tumor registration in the Swedish Cancer Register and Inpatient Register between 1990 and 2014

Giorgio Tettamanti,1 Rickard Ljung,1 Anders Ahlbom,1 Mats Talbäck,1 Birgitta Lannering,2 Tiit Mathiesen,3,4 Jenny Pettersson Segerlind,3 Maria Feychting1 1Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Pediatric Oncology, Department of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden; 3Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 4Department of Clinical Medicine, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark Background: The Swedish Cancer Register (SCR) is characterized by excellent quality and completeness overall, but the quality of the reporting may vary according to tumor site and age, and may change over time. The aim of the current study was to investigate the completeness of the reporting of central nervous system (CNS) tumor cases to the SCR. Materials and methods: Individuals hospitalized for a CNS tumor between 1990 and 2014 were identified using the Inpatient Register; the proportion of identified cases that did not have any cancer diagnosis reported to the SCR was subsequently assessed. Results: Between 1990 and 2014, 58,698 individuals were hospitalized for a CNS tumor, and a large proportion of them did not have any cancer diagnosis reported to the SCR (26%). This discrepancy was particularly pronounced for benign tumors and among elderly patients (over 30%). It was substantially lower for malignant brain tumors among adults (10%); moreover, no increase in the discrepancy between the two registers was observed in this group during the study period. Similar findings were found when assessing the concordance between the Cause of Death Register and the SCR. Among CNS tumor patients who were not reported to the SCR, a large proportion had only one hospital discharge diagnosis containing a CNS tumor (35%) and were less likely to be found in the Outpatient Register, which indicates that a large proportion of patients may have received an erroneous diagnosis. Conclusion: While a large proportion of CNS tumor patients were not reported to the SCR, the discrepancy between the SCR and the Inpatient Register was relatively small for malignant brain tumors among adults and has remained stable throughout the study period. We do not recommend that data from the Inpatient Register are combined with the SCR to estimate CNS tumor incidence, without proper confirmation of the diagnoses, as a considerable proportion of CNS tumor diagnoses registered in the Inpatient Register is unlikely to reflect true CNS tumors. Keywords: brain neoplasms, central nervous system neoplasms, registries, Swede

Late mortality among survivors of childhood acute lymphoblastic leukemia diagnosed during 1971–2008 in Denmark, Finland, and Sweden : A population-based cohort study

Objective: Investigate all-cause and cause-specific late mortality after childhood acute lymphoblastic leukemia (ALL) in a population-based Nordic cohort. Methods: From the cancer registries of Denmark, Finland, and Sweden, we identified 3765 five-year survivors of ALL, diagnosed before age 20 during 1971–2008. For each survivor, up to five matched comparison subjects were randomly selected from the general population (n = 18,323). Causes of death were classified as relapse related, health related, and external. Late mortality was evaluated by cumulative incidences of death from 5-year survival date. Mortality hazard ratios (HR) were evaluated with Cox proportional models. Results: Among the survivors, 315 deaths occurred during a median follow-up of 16 years from 5-year survival date (range 0–42). The majority were attributable to relapse (n = 224), followed by second neoplasm (n = 45). Cumulative incidence of all-cause late mortality at 15 years from diagnosis decreased gradually over treatment decades, from 14.4% (95% confidence interval [CI]: 11.6–17.2) for survivors diagnosed during 1971–1981, to 2.5% (95% CI: 1.3–3.7) for those diagnosed during 2002–2008. This was mainly attributable to a reduction in relapse-related deaths decreasing from 13.4% (95% CI: 10.7–16.1) for survivors diagnosed during 1971–1981 to 1.9% (95% CI: 0.9–2.8) for those diagnosed during 2002–2008. Health-related late mortality was low and did not change substantially across treatment decades. Compared to comparison subjects, all-cause mortality HR was 40 (95% CI: 26–61) 5–9 years from diagnosis, and 4.4 (95% CI: 3.4–5.6) ≥10 years from diagnosis. Conclusions: Survivors of ALL have higher late mortality than population comparison subjects. Among the survivors, there was a temporal reduction in risk of death from relapse, without increments in health-related death