Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). ...These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk. Since empirical evidence is lacking in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome and other CSS. Moreover, tuberous sclerosis complex, von Hippel-Lindau disease, neurofibromatosis type 1 and other CSS do not meaningfully confound RRs for brain tumors. Empirical data on the use of CT scans among CSS patients is urgently needed. Our assessment indicates that associations with radiation exposure from pediatric CT scans and leukemia or brain tumors reported in previous studies are unlikely to be substantially confounded by unmeasured CSS.
It is established that moderate-to-high doses of ionising radiation increase the risk of subsequent cancer in the exposed individual, but the question arises as to the risk of cancer from higher ...doses, such as those delivered during radiotherapy, accidents, or deliberate acts of malice. In general, the cumulative dose received during a course of radiation treatment is sufficiently high that it would kill a person if delivered as a single dose to the whole body, but therapeutic doses are carefully fractionated and high/very high doses are generally limited to a small tissue volume under controlled conditions. The very high cumulative doses delivered as fractions during radiation treatment are designed to inactivate diseased cells, but inevitably some healthy cells will also receive high/very high doses. How the doses (ranging from <1 Gy to tens of Gy) received by healthy tissues during radiotherapy affect the risk of second primary cancer is an increasingly important issue to address as more cancer patients survive the disease. Studies show that, except for a turndown for thyroid cancer, a linear dose-response for second primary solid cancers seems to exist over a cumulative gamma radiation dose range of tens of gray, but with a gradient of excess relative risk (ERR) per Gy that varies with the type of second cancer, and which is notably shallower than that found in the Japanese atomic bomb survivors receiving a single moderate-to-high acute dose. The risk of second primary cancer consequent to high/very high doses of radiation is likely to be due to repopulation of heavily irradiated tissues by surviving stem cells, some of which will have been malignantly transformed by radiation exposure, although the exact mechanism is not known, and various models have been proposed. It is important to understand the mechanisms that lead to the raised risk of second primary cancers consequent to the receipt of high/very high doses, in particular so that the risks associated with novel radiation treatment regimens - for example, intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) that deliver high doses to the target volume while exposing relatively large volumes of healthy tissue to low/moderate doses, and treatments using protons or heavy ions rather than photons - may be properly assessed.
Patients with head and neck cancer may experience chemoradiotherapy-induced hearing loss, but the weighing of involved variables has been subjective. Identification of patient and treatment ...characteristics to predict the absolute posttreatment hearing level is important for effective counseling of patients undergoing chemoradiotherapy.
To predict treatment-induced hearing loss among patients with head and neck cancer.
A retrospective cohort study was performed at The Netherlands Cancer Institute. One hundred and fifty-six patients with head and neck cancer treated with concomitant chemoradiotherapy as the primary treatment modality from January 1, 1997, through December 31, 2011, were enrolled. Follow-up was complete on March 1, 2012, and data were analyzed from April 1, 2011, through November 5, 2013.
High-dose intravenously administered cisplatin-based concomitant chemoradiotherapy. Cisplatin, 100 mg/m2, was administered in 3 courses on days 1, 22, and 43 during 7 weeks of radiotherapy (total radiation dose, 70 Gy in 35 fractions).
Posttreatment bone conduction hearing threshold at pure-tone average frequencies of 1, 2, and 4 kHz, based on pure-tone audiometry after completion of treatment. Predictors included baseline hearing levels, radiation dose to the cochlea, and cisplatin dose. A multilevel mixed-effects linear regression model for predicting whether or not posttreatment hearing was at least 35 dB was established, and cross-validated sensitivity and specificity were obtained.
Of 156 patients who received high-dose concomitant chemoradiotherapy, 15 were missing the exact radiation dose to the cochlea and 41 had no data on posttreatment pure-tone audiometry. Nineteen patients had a hearing level of at least 35 dB for at least 1 ear before the treatment. The remaining 81 patients (162 ears) had a total cumulative cisplatin dose ranging from 315 to 600 (median, 546) mg. The radiation dose to the cochlea ranged from 1.1 to 70.9 (median, 13.6) Gy. Based on data from the 81 patients (162 ears), the area under the receiver operating characteristic curve was 0.68, with a sensitivity of 29% (95% CI, 13%-51%) and a specificity of 97% (95% CI, 88%-100%), resulting in a positive predictive value of 78%.
Patient and treatment characteristics can be used to predict hearing level after concomitant chemoradiotherapy for head and neck cancer. This step may constitute the first in evidence-based individual counseling for treatment-induced hearing loss.
Few studies have examined whether modern radiotherapy and chemotherapy affect the risk of contralateral breast cancer (CBC), and results are inconclusive.
We assessed long-term risk of CBC in a ...predominantly young breast cancer (BC) population (n = 7,221), focusing on the effects of radiation dose, chemotherapy, and family history of BC. Risk of CBC was evaluated using Cox proportional hazards regression models.
Radiotherapy-associated risk of CBC increased with decreasing age at first treatment (age < 35 years, hazard ratio HR = 1.78; 95% CI, 0.85 to 3.72; age > 45 years, HR = 1.09; 95% CI, 0.82 to 1.45). Postmastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than postlumpectomy radiotherapy using tangential fields. Women treated before age 45 years with postlumpectomy radiotherapy experienced 1.5-fold increased risk of CBC compared with those who had postmastectomy radiotherapy. The joint effects of postlumpectomy radiotherapy and strong family history for BC on risk of CBC were greater than expected when individual risks were summed (HR = 3.52; 95% CI, 2.07 to 6.02; P(departure from additivity) = .043). Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was associated with a nonsignificantly decreased risk of CBC in the first 5 years of follow-up but did not reduce CBC risk in subsequent years.
Young patients with BC irradiated with breast tangentials experience increased risk of CBC, especially in those with a positive family history of BC. This finding should be taken into account when advising breast radiation with tangential fields to young patients with BC. Adjuvant chemotherapy seemed to reduce the risk of CBC during the first 5 years after treatment only.
Computed tomography (CT) scans are indispensable in modern medicine; however, the spectacular rise in global use coupled with relatively high doses of ionizing radiation per examination have raised ...radiation protection concerns. Children are of particular concern because they are more sensitive to radiation-induced cancer compared with adults and have a long lifespan to express harmful effects which may offset clinical benefits of performing a scan. This paper describes the design and methodology of a nationwide study, the Dutch Pediatrie CT Study, regarding risk of leukemia and brain tumors in children after radiation exposure from CT scans. It is a retrospective recordlinkage cohort study with an expected number of 100,000 children who received at least one electronically archived CT scan covering the calendar period since the introduction of digital archiving until 2012. Information on all archived CT scans of these children will be obtained, including date of examination, scanned body part and radiologist's report, as well as the machine settings required for organ dose estimation. We will obtain cancer incidence by record linkage with external databases. In this article, we describe several approaches to the collection of data on archived CT scans, the estimation of radiation doses and the assessment of confounding. The proposed approaches provide useful strategies for data collection and confounder assessment for general retrospective record-linkage studies, particular those using hospital databases on radiological procedures for the assessment of exposure to ionizing or non-ionizing radiation.
•In a population-based setting we studied brain structure before cancer diagnosis.•Brain structure was not altered before non-CNS cancer diagnosis.•The effect of cancer on the brain before clinical ...manifestation is not supported.
Many studies have shown that patients with non-central nervous system (CNS) cancer can have brain abnormalities, such as reduced gray matter volume and cerebral microbleeds. These abnormalities can sometimes be present even before start of treatment, suggesting a potential detrimental effect of non-CNS cancer itself on the brain. In these previous studies, psychological factors associated with a cancer diagnosis and selection bias may have influenced results. To overcome these limitations, we investigated brain structure with magnetic resonance imaging (MRI) prior to cancer diagnosis.
Between 2005 and 2014, 4,622 participants from the prospective population-based Rotterdam Study who were free of cancer, dementia, and stroke, underwent brain MRI and were subsequently followed for incident cancer until January 1st, 2015. We investigated the association between brain MRI measurements, including cerebral small vessel disease, volumes of global brain tissue, lobes, and subcortical structures, and global white matter microstructure, and the risk of non-CNS cancer using Cox proportional hazards models. Age was used as time scale. Models were corrected for e.g. sex, intracranial volume, educational level, body mass index, hypertension, diabetes mellitus, smoking status, alcohol use, and depression sum-score.
During a median (interquartile range) follow-up of 7.0 years (4.9–8.1), 353 participants were diagnosed with non-CNS cancer. Results indicated that persons who develop cancer do not have more brain abnormalities before clinical manifestation of the disease than persons who remain free of cancer. The largest effect estimates were found for the relation between presence of lacunar infarcts and the risk of cancer (hazard ratio HR 95% confidence interval CI = 1.39 0.97–1.98) and for total brain volume (HR 95%CI per standard deviation increase in total brain volume = 0.76 0.55–1.04).
We did not observe associations between small vessel disease, brain tissue volumes, and global white matter microstructure, and subsequent cancer risk in an unselected population. These findings deviate from previous studies indicating brain abnormalities among patients shortly after cancer diagnosis.
•Estimates were made of number of patients likely receiving cumulative effective dose ≥100 mSv in 5-years from CT exams.•It results in about 2.5 million patients in 35 OECD countries.•Countries were ...classified into Low: 0 to <1, Medium: 1 to <2 and High: ≥2 patients with CED ≥ 100 mSv/1000 population.•There are 2 countries in Low, 24 in medium and 9 in high number group.•Stake holders in patient radiation safety should attend to the issue of high doses to such large number of patients.
To estimate the number of patients in OECD (Organization for Economic Co-operation and Development) countries who receive a cumulative effective dose (CED) ≥ 100 mSv from recurrent computed tomography (CT) exams.
Taking into account recently published data on the number of CTs per patient and the fraction of patients with CED ≥ 100 mSv as well as country-specific data for the number of CT exams/1,000 population from OECD publication, this paper makes estimations for 35 OECD countries.
The estimated total number of patients with CED ≥ 100 mSv for all 35 OECD countries combined in a 5-year period is around 2.5 million (2,493,685) in a population of 1.2 billion (1,176,641,900), i.e., 0.21% of the population. Expressed per 1,000 population, the range is from 0.51 for Finland to 2.94 for the US, a nearly six-fold difference. Countries with more than 2 patients with CED ≥ 100 mSv in a 5-yr period per 1,000 population are: Belgium, France, Iceland, Japan, Korea, Luxembourg, Portugal, Turkey, and US.
The first estimates of the number of patients likely receiving CED ≥ 100 mSv through recurrent CT exams in 35 OECD countries indicate that 2.5 million patients reach this level in a 5-year period. There is an urgent need for various stakeholders including medical physicists, referring physicians, health policy makers, manufacturers of CT equipment and epidemiologists to attend to the issue in the interest of patient radiation safety.
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