Is there Unmeasured Indication Bias in Radiation-Related Cancer Risk Estimates from Studies of Computed Tomography?

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Abstract

<p class="first" id="P1">Recently reported studies have associated radiation exposure from computed tomography (CT) scanning with small excess cancer risks. However, since existing medical records were used in these studies, they could not control for reasons for the CT scans and therefore, the results may have been confounded by indication. Here we conducted a study to estimate potential indication bias that could affect hazard ratios for colorectal, lung and female breast cancers by reasons for a CT scan. This involved a retrospective cohort study of electronic records from all patients aged 18–89 years without previous cancer diagnoses, who received at least one CT scan at Columbia University Medical Center in the period of 1994–2014. This investigation is not a study of CT-related cancer risks with adjustment for reasons, but an evaluation of the potential for confounding by indication in such studies. Among 75,968 patients, 212,487 CT scans were analyzed during a mean follow-up of 7.6 years. For colorectal and female breast cancers, no hazard ratio bias estimates for any of the CT reasons reached statistical significance. For lung cancer, significant biases occurred only in patients with unknown CT reasons and in patients with CTs for “abnormal findings” and in those with CTs for cancer- or nodule-related reasons. This retrospective cohort study among adults with ≥1 CT scan evaluates, for the first time, CT reason-specific indication biases of potential CT-related cancer risks. Overall, our data suggest that, in studies of adults who underwent CT scans, indication bias is likely to be of negligible importance for colorectal cancer and female breast cancer risk estimation; for lung cancer, indication bias is possible but would likely be associated with only a small modulation of the risk estimate. </p>

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Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study

Mark S. Pearce, Jane Salotti, Mark Little … (2012)

Summary Background Although CT scans are very useful clinically, potential cancer risks exist from associated ionising radiation, in particular for children who are more radiosensitive than adults. We aimed to assess the excess risk of leukaemia and brain tumours after CT scans in a cohort of children and young adults. Methods In our retrospective cohort study, we included patients without previous cancer diagnoses who were first examined with CT in National Health Service (NHS) centres in England, Wales, or Scotland (Great Britain) between 1985 and 2002, when they were younger than 22 years of age. We obtained data for cancer incidence, mortality, and loss to follow-up from the NHS Central Registry from Jan 1, 1985, to Dec 31, 2008. We estimated absorbed brain and red bone marrow doses per CT scan in mGy and assessed excess incidence of leukaemia and brain tumours cancer with Poisson relative risk models. To avoid inclusion of CT scans related to cancer diagnosis, follow-up for leukaemia began 2 years after the first CT and for brain tumours 5 years after the first CT. Findings During follow-up, 74 of 178 604 patients were diagnosed with leukaemia and 135 of 176 587 patients were diagnosed with brain tumours. We noted a positive association between radiation dose from CT scans and leukaemia (excess relative risk [ERR] per mGy 0·036, 95% CI 0·005–0·120; p=0·0097) and brain tumours (0·023, 0·010–0·049; p<0·0001). Compared with patients who received a dose of less than 5 mGy, the relative risk of leukaemia for patients who received a cumulative dose of at least 30 mGy (mean dose 51·13 mGy) was 3·18 (95% CI 1·46–6·94) and the relative risk of brain cancer for patients who received a cumulative dose of 50–74 mGy (mean dose 60·42 mGy) was 2·82 (1·33–6·03). Interpretation Use of CT scans in children to deliver cumulative doses of about 50 mGy might almost triple the risk of leukaemia and doses of about 60 mGy might triple the risk of brain cancer. Because these cancers are relatively rare, the cumulative absolute risks are small: in the 10 years after the first scan for patients younger than 10 years, one excess case of leukaemia and one excess case of brain tumour per 10 000 head CT scans is estimated to occur. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionising radiation, should be considered if appropriate. Funding US National Cancer Institute and UK Department of Health.

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Cancer risk in 680 000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians

John D Mathews, Anna V Forsythe, Zoe Brady … (2013)

Objective To assess the cancer risk in children and adolescents following exposure to low dose ionising radiation from diagnostic computed tomography (CT) scans. Design Population based, cohort, data linkage study in Australia. Cohort members 10.9 million people identified from Australian Medicare records, aged 0-19 years on 1 January 1985 or born between 1 January 1985 and 31 December 2005; all exposures to CT scans funded by Medicare during 1985-2005 were identified for this cohort. Cancers diagnosed in cohort members up to 31 December 2007 were obtained through linkage to national cancer records. Main outcome Cancer incidence rates in individuals exposed to a CT scan more than one year before any cancer diagnosis, compared with cancer incidence rates in unexposed individuals. Results 60 674 cancers were recorded, including 3150 in 680 211 people exposed to a CT scan at least one year before any cancer diagnosis. The mean duration of follow-up after exposure was 9.5 years. Overall cancer incidence was 24% greater for exposed than for unexposed people, after accounting for age, sex, and year of birth (incidence rate ratio (IRR) 1.24 (95% confidence interval 1.20 to 1.29); P<0.001). We saw a dose-response relation, and the IRR increased by 0.16 (0.13 to 0.19) for each additional CT scan. The IRR was greater after exposure at younger ages (P<0.001 for trend). At 1-4, 5-9, 10-14, and 15 or more years since first exposure, IRRs were 1.35 (1.25 to 1.45), 1.25 (1.17 to 1.34), 1.14 (1.06 to 1.22), and 1.24 (1.14 to 1.34), respectively. The IRR increased significantly for many types of solid cancer (digestive organs, melanoma, soft tissue, female genital, urinary tract, brain, and thyroid); leukaemia, myelodysplasia, and some other lymphoid cancers. There was an excess of 608 cancers in people exposed to CT scans (147 brain, 356 other solid, 48 leukaemia or myelodysplasia, and 57 other lymphoid). The absolute excess incidence rate for all cancers combined was 9.38 per 100 000 person years at risk, as of 31 December 2007. The average effective radiation dose per scan was estimated as 4.5 mSv. Conclusions The increased incidence of cancer after CT scan exposure in this cohort was mostly due to irradiation. Because the cancer excess was still continuing at the end of follow-up, the eventual lifetime risk from CT scans cannot yet be determined. Radiation doses from contemporary CT scans are likely to be lower than those in 1985-2005, but some increase in cancer risk is still likely from current scans. Future CT scans should be limited to situations where there is a definite clinical indication, with every scan optimised to provide a diagnostic CT image at the lowest possible radiation dose.