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Yarmoshenko, Ilia V., and Georgy P. Malinovsky. "Lung cancer mortality and radon exposure in Russia." Nukleonika 61, no. 3 (September 1, 2016): 263–68. http://dx.doi.org/10.1515/nuka-2016-0044.
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Abstract The association between the lung cancer and indoor radon exposure in Russian population was investigated. The average indoor radon concentration for each region was estimated using the annual reports issued by the Saint-Petersburg Ramzaev Research Institute of Radiation Hygiene for the period 2008–2013. The average standardized lung cancer mortalities among males and females were estimated using the reports of the Moscow Hertzen Cancer Research Institute for the period 2008–2012. The relative risk (RR) was estimated as a ratio between the average mortality within seven exposure intervals and background mortality. The slope factors of linear dependence between the indoor radon exposure and lung cancer RR are 0.026 (−0.11÷0.17) and 0.83 (0.52–1.12) per radon concentration 100 Bq/m3 for males and females, respectively (with 90% confidence interval). The obtained results can be explained by the confounding effect of tobacco smoking. Significant excess risk of lung cancer in female population can be associated with radon exposure and low prevalence of smoking.
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Hauptmann, Michael, Robert D. Daniels, Elisabeth Cardis, Harry M. Cullings, Gerald Kendall, Dominique Laurier, Martha S. Linet, et al. "Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis." JNCI Monographs 2020, no. 56 (July 1, 2020): 188–200. http://dx.doi.org/10.1093/jncimonographs/lgaa010.
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Abstract Background Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. Methods Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006–2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. Results Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. Conclusions Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.
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Dietz, Andrew Charles, Kristy Seidel, Wendy M. Leisenring, Daniel A. Mulrooney, Jean M. Tersak, Richard D. Glick, Cathy A. Burnweit, et al. "Solid organ transplant after treatment for childhood cancer: A report from the Childhood Cancer Survivor Study." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10559. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10559.
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10559 Background: Childhood cancer therapy is associated with late onset, organ-specific impairment. However, the prevalence of and outcomes after solid organ transplant (SOT) in childhood cancer survivors (CCS) are unknown. Methods: Data on U.S-based participants in the Childhood Cancer Survivor Study were linked with the Organ Procurement and Transplantation Network. Cumulative incidence of transplant (CIT) 35 years after cancer diagnosis, multivariable Cox regression models for hazard ratios (HR), Kaplan-Meier (KM) survival and corresponding 95% confidence intervals (CI) were estimated. Results: Among 13,318 survivors, median follow-up age 39 years (interquartile range, IQR 33-46), and median time since cancer diagnosis 31 years (IQR 28-36 years), 100 CCS had SOT after study entry with characteristics and outcomes provided (table). Conclusions: Organ-specific radiation and chemotherapy exposure increase the risk for SOT after childhood cancer. Five-year survival rates after renal and cardiac SOT are favorable. [Table: see text]
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Krestinina, L. Yu, S. A. Shalaginov, S. S. Silkin, S. B. Epifanova, and A. V. Akleyev. "Radiogenic risk of solid cancer incidence in persons exposed to radiation in childhood in the Southern Urals." Radiatsionnaya Gygiena = Radiation Hygiene 14, no. 1 (April 15, 2021): 49–59. http://dx.doi.org/10.21514/1998-426x-2021-14-1-49-59.
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The aim of this work is to assess the radiogenic risk of solid cancers incidence in the members of the Urals Childhood Exposure Cohort. The cohort includes people exposed under 20 years of age as a result of two radiation accidents at the Mayak Production Association in the Southern Urals (discharges of radioactive waste into the Techa River and the formation of the East Ural radioactive trace). The number of the cohort for solid cancer incidence analysis is 31,578 individuals. All the members were postnatally exposed and some of them – in-utero. Some of their parents were exposed before conception. 2,018 solid cancers were registered on the incidence catchment area during the period 1956-2018, the total amount of person years was 818,083. The analysis was carried out by the Poisson regression method with a simple parametric excess relative risk model. 95% confidence intervals were estimated with maximum likelihood approach. Only a postnatal dose was used in the first solid cancer incidence analysis of this cohort members with due account for preconception exposure of parents. TRDS-2016 mean postnatal dose accumulated over the entire follow-up period in the stomach of cohort members was 0.047 Gy. The analysis showed linear dependence of solid cancer incidence excess relative risk on postnatal dose. Excess relative risk was 0.66/Gy, р=0.006 with a five-year latency period. While estimating excess relative risk in different age groups at the beginning of exposure, a significant risk was present only in the age group under 1 year and amounted to 2.16/Gy; р<0.02 at the onset of exposure. The present results are in agreement with the results of the solid cancer incidence risk analysis both in the Techa River Cohort of exposed In-Utero where a statistically significant excess relative risk from a postnatal dose was revealed, and with the results of risk analysis in the Japanese cohort of people exposed in-utero and in early childhood.
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Yokota, Kenichi, Mariko Mine, Hisayoshi Kondo, Naoki Matsuda, Yoshisada Shibata, and Noboru Takamura. "Cancer mortality in residents of the terrain-shielded area exposed to fallout from the Nagasaki atomic bombing." Journal of Radiation Research 59, no. 1 (September 26, 2017): 1–9. http://dx.doi.org/10.1093/jrr/rrx047.
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Abstract The health effects of radiation exposure from the atomic bomb fallout remain unclear. The objective of the present study is to elucidate the association between low-dose radiation exposure from the atomic bomb fallout and cancer mortality among Nagasaki atomic bomb survivors. Of 77 884 members in the Nagasaki University Atomic Bomb Survivors Cohort, 610 residents in the terrain-shielded area with fallout were selected for this analysis; 1443 residents in the terrain-shielded area without fallout were selected as a control group; and 3194 residents in the direct exposure area were also selected for study. Fifty-two deaths due to cancer in the terrain-shielded fallout area were observed during the follow-up period from 1 January 1970 to 31 December 2012. The hazard ratio for cancer mortality in the terrain-shielded fallout area was 0.90 (95% confidence interval: 0.65–1.24). No increase in the risk of cancer mortality was observed, probably because the dose of the radiation exposure was low for residents in the terrain-shielded fallout areas of the Nagasaki atomic bomb, and also because the number of study subjects was small.
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Weil, Brent, Arin L. Madenci, Qi Liu, Todd M. Gibson, Yutaka Yasui, Joseph Philip Neglia, Wendy M. Leisenring, et al. "Infection related late mortality in survivors of childhood cancer with asplenia or radiation-induced hyposplenism: A report from the Childhood Cancer Survivor Study." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10563. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10563.
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10563 Background: Asplenia or hyposplenism can develop in survivors of childhood cancer following splenectomy or radiotherapy exposure to the left upper quadrant of the abdomen (LUQ). Knowledge regarding long-term infection related outcomes for these survivors is limited. Methods: Infection related late mortality (sepsis, meningitis or pneumonia) was evaluated in 20,805 5-year survivors (diagnosed <21 years of age from 1970-1999, median follow-up 26 years, range 5-44) using cumulative incidence and Poisson regression models to calculate adjusted relative risk (RR) and 95% confidence intervals (CI). Average LUQ radiation was calculated as a surrogate for splenic radiation. Results: Treatment included splenectomy for 1328 survivors (6%). An additional 10,295 (49%) were exposed to LUQ radiotherapy without splenectomy. The cumulative incidence of infection related late mortality was 1.4% (95%CI: 0.7%-2.2%) at 35 years after splenectomy and 0.6% (95%CI: 0.4%-0.8%) after LUQ radiotherapy, with a total of 78 deaths attributable to infectious causes (25 sepsis, 1 meningitis, 52 pneumonia). Splenectomy (RR=8.4, p<0.001) and increasing LUQ radiotherapy dose (p<0.001) were independently associated with infection related late mortality (Table). Conclusions: Splenectomy and LUQ radiotherapy increased risk for infection related late mortality. While infectious mortality increased with increasing LUQ radiation dose, even lower dose exposure (<10Gy) increased risk substantially. Accordingly, cancer survivors exposed to LUQ radiotherapy should be considered at risk for functional asplenia and managed similarly to asplenic individuals with respect to vaccinations and febrile illnesses. [Table: see text]
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Sugiyama, Hiromi, Munechika Misumi, Ritsu Sakata, Alina V. Brenner, Mai Utada, and Kotaro Ozasa. "Mortality among individuals exposed to atomic bomb radiation in utero: 1950–2012." European Journal of Epidemiology 36, no. 4 (January 25, 2021): 415–28. http://dx.doi.org/10.1007/s10654-020-00713-5.
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AbstractWe examined the mortality risks among 2463 individuals who were exposed in utero to atomic bomb radiation in Hiroshima or Nagasaki in August 1945 and were followed from October 1950 through 2012. Individual estimates of mother’s weighted absorbed uterine dose (DS02R1) were used. Poisson regression method was used to estimate the radiation-associated excess relative risk per Gy (ERR/Gy) and 95% confidence intervals (CI) for cause-specific mortality. Head size, birth weight, and parents’ survival status were evaluated as potential mediators of radiation effect. There were 339 deaths (216 males and 123 females) including deaths from solid cancer (n = 137), lymphohematopoietic cancer (n = 8), noncancer disease (n = 134), external cause (n = 56), and unknown cause (n = 4). Among males, the unadjusted ERR/Gy (95% CI) was increased for noncancer disease mortality (1.22, 0.10–3.14), but not for solid cancer mortality (− 0.18, < − 0.77–0.95); the unadjusted ERR/Gy for external cause mortality was not statistically significant (0.28, < − 0.60–2.36). Among females, the unadjusted ERRs/Gy were increased for solid cancer (2.24, 0.44–5.58), noncancer (2.86, 0.56–7.64), and external cause mortality (2.57, 0.20–9.19). The ERRs/Gy adjusted for potential mediators did not change appreciably for solid cancer mortality, but decreased notably for noncancer mortality (0.39, < − 0.43–1.91 for males; 1.48, − 0.046–4.55 for females) and external cause mortality (0.10, < − 0.57–1.96 for males; 1.38, < − 0.46–5.95 for females). In conclusion, antenatal radiation exposure is a consistent risk factor for increased solid cancer mortality among females, but not among males. The effect of exposure to atomic bomb radiation on noncancer disease and external cause mortality among individuals exposed in utero was mediated through small head size, low birth weight, and parental loss.
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Ohira, Tetsuya, Hiroki Shimura, Fumikazu Hayashi, Masanori Nagao, Seiji Yasumura, Hideto Takahashi, Satoru Suzuki, et al. "Absorbed radiation doses in the thyroid as estimated by UNSCEAR and subsequent risk of childhood thyroid cancer following the Great East Japan Earthquake." Journal of Radiation Research 61, no. 2 (February 6, 2020): 243–48. http://dx.doi.org/10.1093/jrr/rrz104.
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Abstract The identification of thyroid cancers among children after the Chernobyl nuclear power plant accident propelled concerns regarding long-term radiation effects on thyroid cancer in children affected by the Fukushima Daiichi nuclear power plant accident in Fukushima, Japan. Herein we consider the potential association between absorbed dose in the thyroid and the risk of developing thyroid cancer as detected by ultrasonography on 300 473 children and adolescents aged 0–18 years in Fukushima. The absorbed dose mentioned in the present study indicates the sum of that from external exposure and that from internally deposited radionuclides. We grouped participants according to estimated absorbed doses in each of 59 municipalities in Fukushima Prefecture, based on The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) 2013 report. The 59 municipalities were assigned to quartiles by dose. We limited our analyses to participants aged ≥6 years because only one case of thyroid cancer was observed in participants aged ≤5 years; 164 299 participants were included in the final analysis. Compared with the lowest dose quartile, the age- and sex-adjusted rate ratios (95% confidence intervals) for the low-middle, high-middle and highest quartiles were 2.00 (0.84–4.80), 1.34 (0.50–3.59) and 1.42 (0.55–3.67) for the 6–14-year-old groups and 1.99 (0.70–5.70), 0.54 (0.13–2.31) and 0.51 (0.12–2.15) for the >15-year-old group, respectively. No dose-dependent pattern emerged from the geographical distribution of absorbed doses by municipality, as estimated by UNSCEAR, and the detection of thyroid cancer among participants within 4–6 years after the accident. Ongoing surveillance might further clarify the effects of low-dose radiation exposure on thyroid cancer in Fukushima.
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Meulepas, Johanna M., Cécile M. Ronckers, Anne M. J. B. Smets, Rutger A. J. Nievelstein, Patrycja Gradowska, Choonsik Lee, Andreas Jahnen, et al. "Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands." JNCI: Journal of the National Cancer Institute 111, no. 3 (July 18, 2018): 256–63. http://dx.doi.org/10.1093/jnci/djy104.
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Abstract Background Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood. Methods For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries. Standardized incidence ratios were calculated using cancer incidence rates from the general Dutch population. Excess relative risks (ERRs) per 100 mGy organ dose were calculated with Poisson regression. All statistical tests were two-sided. Results Standardized incidence ratios were elevated for all cancer sites. Mean cumulative bone marrow doses were 9.5 mGy at the end of follow-up, and leukemia risk (excluding myelodysplastic syndrome) was not associated with cumulative bone marrow dose (44 cases). Cumulative brain dose was on average 38.5 mGy and was statistically significantly associated with risk for malignant and nonmalignant brain tumors combined (ERR/100 mGy: 0.86, 95% confidence interval = 0.20 to 2.22, P = .002, 84 cases). Excluding tuberous sclerosis complex patients did not substantially change the risk. Conclusions We found evidence that CT-related radiation exposure increases brain tumor risk. No association was observed for leukemia. Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.
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Rivkind, Nikolai, Valeriy Stepanenko, Irina Belukha, Jamie Guenthoer, Kenneth J. Kopecky, Sergei Kulikov, Irina Kurnosova, et al. "Female breast cancer risk in Bryansk Oblast, Russia, following prolonged low dose rate exposure to radiation from the Chernobyl power station accident." International Journal of Epidemiology 49, no. 2 (October 19, 2019): 448–56. http://dx.doi.org/10.1093/ije/dyz214.
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Abstract Background Ionizing radiation is a known cause of female breast cancer, but there have been few studies of the risk after prolonged radiation exposure at low dose rates. Methods This population-based case-control study estimated breast cancer risk after ∼25 years’ exposure to radiation from the Chernobyl accident. Cases (n = 468) were women ≤55 years old when first diagnosed with invasive breast cancer during October 2008 through February 2013, who lived in Bryansk Oblast, Russia at the time of the accident and their diagnoses. Controls, individually matched to cases on birth year, administrative district of residence and urban vs non-urban settlement during the accident, were women without breast cancer who lived in Bryansk Oblast at the time of the accident and on their cases’ diagnosis dates (n = 468). Subjects were interviewed regarding residence, dietary and food source histories to support individualized estimation of their radiation doses to the breast, which ranged from 0.04 − 41 centigray (cGy) (mean 1.3 cGy). Results In multivariable analyses, the odds ratio for breast cancer risk was 3.0 [95% confidence interval (CI): 1.3, 7.0] and 2.7 (95% CI: 1.0, 7.3) in the seventh and eighth dose octiles, respectively, relative to the lowest octile. Analyses of dose effect modification suggested that radiation-related risk may have been higher in women who were younger at the time of the accident and/or at the time of diagnosis. Conclusions This study suggests that prolonged exposure to ionizing radiation at low dose rates can increase risk of breast cancer.
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Eidemüller, Markus, Erik Holmberg, Marie Lundell, and Per Karlsson. "Evidence for Increased Susceptibility to Breast Cancer From Exposure to Ionizing Radiation Due to a Familial History of Breast Cancer: Results From the Swedish Hemangioma Cohort." American Journal of Epidemiology 190, no. 1 (July 31, 2020): 76–84. http://dx.doi.org/10.1093/aje/kwaa163.
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Abstract Women with a history of breast cancer among family members are at increased risk for breast cancer. However, it is unknown whether a familial breast cancer history (FBCH) also increases individual susceptibility to breast cancer from radiation exposure. In this cohort study, 17,200 female Swedish hemangioma patients with 1,079 breast cancer cases diagnosed between 1958 and 2013, exposed to ionizing radiation in infancy, were linked to their first-degree relatives. The association between FBCH and radiation-induced breast cancer risk was assessed. Further, the relevance for breast cancer radiotherapy and mammography screening was evaluated. On average, the radiation-induced excess relative risk and excess absolute risk of breast cancer at age 50 years were 0.51 Gy−1 (95% confidence interval (CI): 0.33, 0.71) and 10.8 cases/10,000 person-years/Gy (95% CI: 7.0, 14.6), respectively. Radiation risk was higher by a factor of 2.7 (95% CI: 1.0, 4.8; P = 0.05) if 1 first-degree relative was affected by breast cancer. For whole-breast standard radiotherapy at age 40 years with a contralateral breast dose of 0.72 Gy, the 20-year radiation-related excess risk of contralateral breast cancer was estimated to increase from 0.6% for women without FBCH to 1.7% for women with FBCH. In a biennial mammography screening program at ages 40–74 years, radiation risk up to age 80 years would increase from 0.11% for women without FBCH to 0.29% for women with FBCH.
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Azizova, Tamara V., Maria V. Bannikova, Evgeniya S. Grigoryeva, Valentina L. Rybkina, and Nobuyuki Hamada. "Occupational exposure to chronic ionizing radiation increases risk of Parkinson's disease incidence in Russian Mayak workers." International Journal of Epidemiology 49, no. 2 (November 13, 2019): 435–47. http://dx.doi.org/10.1093/ije/dyz230.
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Abstract Background Patients receiving radiotherapy demonstrate cognitive deficits, impairment of neurogenesis and neurovascular damage developing as late side effects of radiation exposure to the head. In light of the increasing use of diagnostic radiological procedures, epidemiological data raise concerns about possible harmful effects of low-level radiation on the human brain. A series of studies of chronically exposed Russian nuclear workers have provided information on risks of cancer and non-cancer diseases. Methods This study aimed to assess the risk of Parkinson’s-disease (PD) incidence in a cohort of workers occupationally exposed to chronic radiation. The cohort comprised workers of a Russian nuclear production facility who were first employed in 1948–1982 and followed up until the end of 2013 (22 377 individuals; 25% female). Using the AMFIT module of EPICURE software, relative risk and excess relative risk per unit dose (ERR/Gy) were calculated based on maximum likelihood. Results A linear association was found between PD incidence and cumulative γ-dose after adjusting for sex and attained age [ERR/Gy = 1.02 (95% confidence interval, 0.59 to 1.63, p = 5.44 × 10–5)]. The ERR/Gy of external radiation for PD incidence was stable after adjusting for neutron dose (ERR/Gy = 1.03; 95% confidence interval: 0.59 to 1.67, p = 6.86 × 10–5). The risk increased with increasing lag period and decreased notably after adjusting for body mass index, smoking and alcohol consumption. Additional adjustments for hypertension, gout, gastric ulcer, head injuries with loss of awareness and diabetes mellitus did not affect the risk estimate. Conclusions This study is the first to suggest that PD is associated with prolonged occupational external γ-ray exposure.
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Olsen, Morten, Ester Garne, Claus Sværke, Lars Søndergaard, Henrik Nissen, Henrik Ø. Andersen, Vibeke E. Hjortdal, Søren P. Johnsen, and Jørgen Videbæk. "Cancer risk among patients with congenital heart defects: a nationwide follow-up study." Cardiology in the Young 24, no. 1 (January 18, 2013): 40–46. http://dx.doi.org/10.1017/s1047951112002144.
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AbstractObjectiveWe aimed to assess cancer risk in congenital heart defect patients, with and without Down's syndrome, compared with the general population.MethodsWe identified all patients born and diagnosed with congenital heart defects from 1977 to 2008 using the Danish National Registry of Patients, covering all Danish hospitals. We compared cancer incidence in the congenital heart defect cohort with that expected in the general population (∼5.5 million) using the Danish Cancer Registry, and computed age- and gender-standardised incidence ratios.ResultsWe identified 15,905 congenital heart defect patients, contributing a total of 151,172 person-years at risk; the maximum length of follow-up was 31 years (median 8 years). In all, 53 patients were diagnosed with cancer, including 30 female and 23 male patients (standardised incidence ratio = 1.63; 95% confidence interval: 1.22–2.13). Risks were increased for leukaemia, brain tumours, and basal cell carcinoma. After excluding 801 patients with Down's syndrome, the standardised incidence ratio was 1.19 (95% confidence interval: 0.84–1.64). In the subgroup of 5660 non-Down's syndrome patients undergoing cardiac surgery or catheter-based interventions, the standardised incidence ratio was 1.45 (95% confidence interval: 0.86–2.29).ConclusionThe overall risk of cancer among congenital heart defect patients without Down's syndrome was not statistically significantly elevated. Cancer risk in the congenital heart defect cohort as a whole, including patients with Down's syndrome, was increased compared with the general population, although the absolute risk was low. Studies with longer follow-up and more information on radiation doses are needed to further examine a potential cancer risk associated with diagnostic radiation exposure.
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Han, Yueh-Ying, Oren Berkowitz, Evelyn Talbott, Douglas Kondziolka, Maryann Donovan, and L. Dade Lunsford. "Are frequent dental x-ray examinations associated with increased risk of vestibular schwannoma?" Journal of Neurosurgery 117, Special_Suppl (December 2012): 78–83. http://dx.doi.org/10.3171/2012.5.gks12615.
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Object The authors evaluated the potential role of environmental risk factors, including exposure to diagnostic or therapeutic radiation and to wireless phones that emit nonionizing radiation, in the etiology of vestibular schwannoma (VS). Methods A total of 343 patients with VSs who underwent Gamma Knife surgery performed between 1997 and 2007 were age and sex matched to 343 control patients from the outpatient degenerative spinal disorders service at the University of Pittsburgh Medical Center. The authors obtained information on previous exposure to medical radiation, use of wireless phone technologies, and other environmental factors thought to be associated with the development of a VS. Conditional multivariate logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results After adjusting for race, education, cigarette smoking, alcohol consumption, occupational exposure to noise, use of cell phones, and family history of cancer, the authors identified only a single factor that was associated with a higher risk of VS: individuals exposed to dental x-rays once a year (aOR = 2.27, 95% CI = 1.01–5.09) or once every 2–5 years (aOR = 2.65, 95% CI = 1.20–5.85), compared with those exposed less than once every 5 years. Of interest, a history of exposure to radiation related to head or head-and-neck computed tomography was associated with a reduced risk of VS (aOR = 0.52, 95% CI = 0.30–0.90). No relationship was found between the use of cell phones or cordless phones and VS. Conclusions Patients with acoustic neuromas reported significantly more exposure to dental x-rays than a matched cohort control group. Reducing the frequency of dental x-ray examinations may decrease the potential risk of VS.
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Mulrooney, Daniel A., Geehong Hyun, Kirsten K. Ness, Matthew J. Ehrhardt, Yutaka Yasui, Daniel Duprez, Rebecca M. Howell, et al. "Cardiac events in survivors of childhood cancer treated in more recent eras: A report from the Childhood Cancer Survivor Study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 10058. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.10058.
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10058 Background: Contemporary cancer protocols have incorporated modifications to minimize cardiotoxic exposures and preserve long-term health. We investigated the impact of these changes on late cardiac outcomes in a large cohort of adult survivors of childhood cancer. Methods: Congestive heart failure (CHF), myocardial infarction (MI), valvular disease, pericardial disease, and arrhythmias were graded by the National Cancer Institute’s Common Terminology Criteria for Adverse Events among 23,462 five-year cancer survivors [6,193 (26%) treated in the 1970s, 9,363 (40%) in the 1980s, and 7,906 (34%) in the 1990s] and 5,057 siblings. Cumulative incidence and 95% confidence intervals (95% CI) were estimated by treatment decade. Adjusted multivariable subdistribution hazard models were used to estimate hazard ratios (HR) and 95% CI for cardiac outcomes by decade. Mediation analysis examined risks with and without cardiotoxic exposures. Results: For survivors [median age 6 years (range: 0-21) at diagnosis, 28 years (8.2-58) at follow-up], cardiac radiation (RT) exposure declined from 77% of those treated in the 1970s to 55% and 40% in the 1980s and 1990s. Anthracycline exposure increased from 28% to 50% to 64%. The 20-year cumulative incidence of CHF (0.69% for those treated in 1970s, 0.74% in the 1980s, 0.54% in the 1990s) and MI (0.38%, 0.24%, 0.19%) declined in more recent treatment eras (p < 0.01). This change was not seen for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%) or arrhythmias (0.08%, 0.09%, 0.13%). Compared to survivors diagnosed in the 1970s, the risk of CHF, MI, and valvular disease decreased in the 1980s and 1990s, but only significantly for MI (HR 0.64 95% CI 0.47-0.89 and 0.52 95% CI 0.32-0.83). The overall MI risk was attenuated by adjustment for cardiac RT exposure (HR 0.94 95% CI 0.80-1.11), mostly among Hodgkin lymphoma (HL) survivors (HR 0.82 95% CI 0.69-0.98 [unadjusted for RT]; 1.03 95% CI 0.83-1.28 [adjusted for RT]). Conclusions: Reductions in exposure to cardiotoxic cancer therapies have resulted in declines in adverse cardiac outcomes, particularly for the RT-associated risk of myocardial infarction among HL survivors.
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Xu, Feng, Ji-Chang Han, Ya-Jun Zhang, Yi-Jie Zhang, Xiao-Chun Liu, Guan-Bin Qi, Dan Liu, Yan-Zhi Chen, Yu-Xia Zhao, and Lu Bai. "Associations ofLIG4andHSPB1Genetic Polymorphisms with Risk of Radiation-Induced Lung Injury in Lung Cancer Patients Treated with Radiotherapy." BioMed Research International 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/860373.
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Objective.This study aims to explore the correlations of genetic polymorphisms inLIG4andHSPB1genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients.Methods.A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs ofLIG4andHSPB1genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0.Results.A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk(P>0.05). Meanwhile, our results revealed that there was no significant association between the frequencies ofLIG4 rs1805388andHSPB1 rs2868371genotype distribution and the risk of RP(P>0.05).Conclusion.In conclusion, we demonstrated that the genetic polymorphisms inLIG4 rs1805388andHSPB1 rs2868371were not obviously correlated with the risk of RP and RILI of lung cancer.
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Wanigaratne, S., E. Holowaty, H. Jiang, TA Norwood, R. Pietrusiak, and R. Brown. "Estimating cancer risk in relation to tritium exposure from routine operation of a nuclear-generating station in Pickering, Ontario." Chronic Diseases and Injuries in Canada 33, no. 4 (September 2013): 247–56. http://dx.doi.org/10.24095/hpcdp.33.4.06.
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Introduction Evidence suggests that current levels of tritium emissions from CANDU reactors in Canada are not related to adverse health effects. However, these studies lack tritium-specific dose data and have small numbers of cases. The purpose of our study was to determine whether tritium emitted from a nuclear-generating station during routine operation is associated with risk of cancer in Pickering, Ontario. Methods A retrospective cohort was formed through linkage of Pickering and north Oshawa residents (1985) to incident cancer cases (1985–2005). We examined all sites combined, leukemia, lung, thyroid and childhood cancers (6–19 years) for males and females as well as female breast cancer. Tritium estimates were based on an atmospheric dispersion model, incorporating characteristics of annual tritium emissions and meteorology. Tritium concentration estimates were assigned to each cohort member based on exact location of residence. Person-years analysis was used to determine whether observed cancer cases were higher than expected. Cox proportional hazards regression was used to determine whether tritium was associated with radiation-sensitive cancers in Pickering. Results Person-years analysis showed female childhood cancer cases to be significantly higher than expected (standardized incidence ratio [SIR] = 1.99, 95% confidence interval [CI]: 1.08–3.38). The issue of multiple comparisons is the most likely explanation for this finding. Cox models revealed that female lung cancer was significantly higher in Pickering versus north Oshawa (HR = 2.34, 95% CI: 1.23–4.46) and that tritium was not associated with increased risk. The improved methodology used in this study adds to our understanding of cancer risks associated with low-dose tritium exposure. Conclusion Tritium estimates were not associated with increased risk of radiation-sensitive cancers in Pickering.
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Morton, Lindsay M., Sophie D. Fossa, Marilyn Stovall, Flora E. van Leeuwen, Tom B. Johannesen, Preetha Rajaraman, Berthe M. Aleman, et al. "Stomach cancer risk following radiotherapy for testicular cancer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4536. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4536.
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4536 Background: Testicular cancer (TC) is a highly curable malignancy occurring most commonly among men aged 15-34 years. Survivors are at increased risk for adverse late effects of therapy. Previous studies have reported more than 4-fold risks of stomach cancer after TC, although the potential role of radiotherapy and chemotherapy for TC in these associations is unclear. Methods: We evaluated stomach cancer risk in an international cohort of 23,982 men diagnosed with TC during 1959-1987. Using detailed radiotherapy records, doses to the stomach tumor location were estimated for 92 stomach cancer patients and 180 individually matched controls. Chemotherapy drugs and doses also were recorded. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. Results: Fifty-seven percent of patients with stomach cancer were diagnosed with TC before age 40 years, 65% had seminoma, 95% had stage I or II disease, and 37% were diagnosed with stomach cancer ≥20 years after TC diagnosis. Patients who received radiotherapy [87 (95%) cases, 151 (84%) controls] had a 5.9-fold (95%CI 1.6-21.3) increased risk of stomach cancer compared with patients who did not receive radiotherapy. Risk increased with increasing radiation dose to the stomach (P-trend<0.001), with ORs of 3.6 (95%CI 1.3-10.6), 4.4 (1.2-16.4) and 13.3 (2.5-70.0) after 20-39.9 Gy, 40-49.9 Gy, and ≥50 Gy radiation to the stomach, respectively, compared with <10 Gy. Radiation-related stomach cancer risk did not vary by calendar year of treatment, age at exposure, or TC histology. The OR for having received any chemotherapy was 1.3 (14 cases, 23 controls, 95% CI 0.6-2.8). Stomach cancer risk was not significantly elevated among patients given cisplatin-based chemotherapy (7 cases, 10 controls, OR=1.7, 95% CI 0.6-5.1). Conclusions: Patients administered radiotherapy for TC in the past are at increased risk of developing stomach cancer, particularly those who received ≥20 Gy to the stomach. The study results warrant consideration in radiation risk assessment and long-term follow-up. Future studies should further investigate a possible role for chemotherapy in stomach cancer risk.
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Whelan, K., A. Mertens, R. Castleberry, P. Mitby, T. Kawashima, C. Sklar, R. Packer, J. Waterbor, J. Blatt, and L. Robison. "Visual complications in childhood cancer survivors: A Childhood Cancer Survivor Study report." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 9006. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.9006.
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9006 Background: The Childhood Cancer Survivor Study (CCSS) is an NIH funded project (U01-CA 55727) designed to study the effects of childhood cancer treatment on long- term survivors. Previous studies have found associations between certain cancer therapies and visual complications. Methods: The CCSS is a retrospective cohort study investigating health outcomes of long-term survivors (> 5 years) diagnosed and treated between 1970 and 1986 compared to a randomly selected sibling cohort. Questionnaires were completed by 14,362 survivors of childhood cancer and 3,901 sibling controls. Analysis determined the first occurrence of 8 visual conditions in 3 time periods: during therapy, end of therapy to 5 years post diagnosis, and greater than or equal to 5 years post diagnosis. Multivariate analyses, adjusting for current age and gender, determined the relative risks (RR) and 95% confidence interval (CI) of visual conditions by treatment exposure. Results: Survivors had statistically significant increases in the RR of cataracts, glaucoma, legal blindness, double vision, retinal condition, and dry eyes, across all time periods, when compared to siblings. During the time period of 5 or more years post-diagnosis, statistically significant positive associations were present for cataracts and other head radiation, craniospinal radiation, total body radiation, and prednisone; glaucoma and craniospinal radiation; double vision and craniospinal radiation; legally blind and other head radiation and craniospinal radiation; and dry eyes and other head radiation, total body radiation, and dexamethasone. There were no statistically significant associations between treatment factors and retinal conditions. Conclusions: Childhood cancer survivors are at risk of developing visual complications and treatment related factors are important determinants of this risk. Follow-up is needed to evaluate the impact of visual conditions on quality of life. [Table: see text] No significant financial relationships to disclose.
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Shah, Shailja C., Paolo Boffetta, Kenneth C. Johnson, Jinfu Hu, Domenico Palli, Monica Ferraroni, Shoichiro Tsugane, et al. "Occupational exposures and odds of gastric cancer: a StoP project consortium pooled analysis." International Journal of Epidemiology 49, no. 2 (January 21, 2020): 422–34. http://dx.doi.org/10.1093/ije/dyz263.
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Abstract Background Gastric cancer pathogenesis represents a complex interaction of host genetic determinants, microbial virulence factors and environmental exposures. Our primary aim was to determine the association between occupations/occupational exposures and odds of gastric cancer. Methods We conducted a pooled-analysis of individual-level data harmonized from 11 studies in the Stomach cancer Pooling Project. Multivariable logistic regression was used to estimate the odds ratio (OR) of gastric cancer adjusted for relevant confounders. Results A total of 5279 gastric cancer cases and 12 297 controls were analysed. There were higher odds of gastric cancer among labour-related occupations, including: agricultural and animal husbandry workers [odds ratio (OR) 1.33, 95% confidence interval (CI): 1.06–1.68]; miners, quarrymen, well-drillers and related workers (OR 1.70, 95% CI: 1.01–2.88); blacksmiths, toolmakers and machine-tool operators (OR 1.41, 95% CI: 1.05–1.89); bricklayers, carpenters and construction workers (OR 1.30, 95% CI: 1.06–1.60); and stationary engine and related equipment operators (OR 6.53, 95% CI: 1.41–30.19). The ORs for wood-dust exposure were 1.51 (95% CI: 1.01–2.26) for intestinal-type and 2.52 (95% CI: 1.46–4.33) for diffuse-type gastric cancer. Corresponding values for aromatic amine exposure were 1.83 (95% CI: 1.09–3.06) and 2.92 (95% CI: 1.36–6.26). Exposure to coal derivatives, pesticides/herbicides, chromium, radiation and magnetic fields were associated with higher odds of diffuse-type, but not intestinal-type gastric cancer. Conclusions Based on a large pooled analysis, we identified several occupations and related exposures that are associated with elevated odds of gastric cancer. These findings have potential implications for risk attenuation and could be used to direct investigations evaluating the impact of targeted gastric cancer prevention/early detection programmes based on occupation.
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Krestinina, L. Yu, S. S. Silkin, L. D. Mikryukova, S. B. Epifanova, and A. V. Akleyev. "Solid cancer incidence risk in in the Ural cohort of the accidentally exposed population: 1956–2017." Radiatsionnaya Gygiena = Radiation Hygiene 13, no. 3 (October 3, 2020): 6–17. http://dx.doi.org/10.21514/1998-426x-2020-13-3-6-17.
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To date, the study of the effects of chronic exposure of the South Ural population has been carried out in two separate cohorts – in the Techa River Cohort and in the East Urals Radioactive Trace Cohort. In 2019, the Ural cohort of accidentally exposed population was formed. It included the population exposed in two radiation situations in the Southern Urals in the 1950s. The number of the combined cohort for the cancer incidence analysis was about 60 thousand people, the follow-up period was extended to 2017, the number of solid cancers was 4537, and the number of person-years was 1283267, which is 3 times more than when analyzing the effects of exposure in each of the two radiation situations separately. In the incidence analysis of all solid cancer types, we used the dose accumulated in the walls of the stomach, which corresponds to the dose accumulated in most organs and tissues with the exception of bone tissue and red bone marrow. The mean dose to the stomach accumulated over the entire follow-up period for cohort members was 38 mGy, the maximum -1.13 Gy. The paper presents the first results of solid cancer incidence risk analysis in the combined cohort, which show a statistically significant dose dependence of the incidence in case of chronic exposure in the range of low and medium doses. The sex and age-averaged excess relative risk value of 0.075/100 mGy (the 95% confidence interval is 0.039–0.113) is comparable to that obtained in the studies of the Japanese cohort of atomic bomb survivors. The statistically significant excess relative risk value of 0.047/100 mGy, obtained separately for men, is in good agreement with that in professional cohorts where men prevail – in the cohort of the Chernobyl NPP accident clean-up workers and in the cohort of professional workers in the three countries (UK, France, USA). The established cohort with a long follow-up period has a great potential for furthermore detailed studies of the effects of radiation and non-radiation factors on public health.
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Gupta, Sumit, Cindy Lau, Bonnie Cooke, Stephen Hall, Paul C. Nathan, and Jason Beyea. "Incidence and predictors of significant hearing loss requiring hearing assistive devices among childhood cancer survivors: A population-based study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 10055. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.10055.
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10055 Background: Though hearing loss is a significant late effect among childhood cancer survivors, recent guidelines note insufficient evidence to quantify natural history or risk associated with specific exposures. We examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HAD) using population-based healthcare data. Methods: In Ontario, Canada, HAD costs are subsidized by the provincial Assistive Devices Program (ADP). Ontario children age <18 years at cancer diagnosis between 1987-2016 were identified using a pediatric cancer registry and linked to ADP claims. The cumulative incidence of HAD use was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined. Results: We identified 11,842 cases and 59,210 matched controls. Cases were at higher risk of HAD [hazard ratio (HR) 12.8, 95% confidence interval (95CI) 9.8-16.7; p<0.001]. The cumulative incidence of HAD among survivors was 2.1% (95CI 1.7-2.5%) at 20-years and 6.4% (95CI 2.8-12.1%) at 30-years. 30-year incidence was highest in survivors of neuroblastoma (10.7%, 95CI 3.8-21.7%) and hepatoblastoma (16.2%, 95CI 8.6-26.0%). Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis (vs. 5-9 years, HR 2.2, 95CI 1.4-3.3; p<0.001). Relative to no cisplatin exposure, patients receiving 1-200mg/m2 were not at greater risk, unlike those receiving higher cumulative doses (Table). Relative to no radiation, those receiving ≤32Gy were at no higher risk, unlike while those receiving >32Gy. Carboplatin exposure was not associated with HAD. Conclusions: Childhood cancer survivors are at elevated risk of requiring HAD which continues to rise between 20 and 30 years from diagnosis. Thresholds of cisplatin and radiation exposure exist above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations. [Table: see text]
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Park, Joong-Won, Moran Ki, Hwa Young Choi, Hyunsoon Cho, Ju Hee Lee, and Young Hwan Koh. "Second cancer risk after diagnostic and monitoring radiation exposure with computed tomography in patients with hepatocellular carcinoma." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 238. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.238.
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238 Background: Contrast-enhanced dynamic computed tomography (CT) is preferred for initial diagnosis and post-treatment monitoring of hepatocellular carcinoma (HCC). The risk of a second cancer with diagnostic and monitoring CT radiation exposure in HCC patients is unclear. Methods: We analyzed cumulative radiation dose (CRD) for diagnostic and monitoring CT with/without transarterial chemoembolization (TACE) in patients with HCC alone (HA group) and HCC patients with a second cancer (SC group), using the big dataset of the National Health Insurance of South Korea. We performed survival analysis, with death treated as a competing risk. Results: A total of 20,073 patients with HCC were enrolled. With a median follow-up of 5.7 years, the SC group comprised 2,005 patients, resulting in a standardized incidence ratio of 1.5 (95% confidence interval [CI], 1.4-1.6) in men and 1.7 (95% CI, 1.6-1.9) in women, as compared with the general population. Use of CT/positron emission tomography (PET) was significantly higher in the SC group (p<0.001). However, the CRD of CT/PET was not significantly different between the SC group and the alive HA group (median effective dose [ED], 93 mSv for the SC group and alive HA group, respectively, p=0.510). After including TACE (n= 9,004 [44.9%], median frequency 2), total CRD was not significantly different between the SC group and the alive HA group. CRD >300 mSv significantly increased the risk of second malignant neoplasms in the subgroup with >7 years of follow-up (YFU) (hazard ratio [HR] 2.01, 95% CI 1.38-2.92, p<0.001). Second cancers in digestive organs and respiratory-intrathoracic organs were significantly increased by CRD in the subgroup with >300 mSv and over 7 YFU (HR 2.41, 95% CI 1.26-4.62; HR 5.69, 95% CI 1.62-20.04, respectively, p<0.01). TACE did not affect the increased risk of second cancers in digestive and respiratory organs in the subgroup >300 mSv and over 7 YFU. Conclusions: The risk of second cancers increased in HCC patients who survived over 7 years with CRD >300 mSv. Consideration of alternative monitoring tests and guidelines for reducing radiation exposure is crucial for long-term HCC survivors.
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Silkin, S., L. Krestinina, and A. Akleev. "Solid Cancer Incidence Risk among the Population Exposed in the East Urals Radioactive Trace over 1957–2014." Medical Radiology and radiation safety 65, no. 4 (November 1, 2020): 58–64. http://dx.doi.org/10.12737/1024-6177-2020-65-4-58-64.
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Purpose: Assessment of solid cancer incidence risk in the cohort of exposed population on the territory of the East Urals radioactive trace over the period of follow-up from 1957 to 2014 with the use of the individual doses provided by the latest TRDS dosimetry system.
Material and methods: The explosion of the liquid radioactive waste storage tank at the «Mayak» Production Association on 29 September 1957 led to the pollution of the territories of the Chelyabinsk and Sverdlovsk Regions and the formation of the EURT, and the population residing on its territory was subjected to protracted chronic external and internal exposure. The analyzed cohort includes 21,384 people, 2,055 of whom received additional radiation before the 1957 accident due to residing in one of the Techa River settlements. The mean dose to the stomach for the members of the EURT cohort was 36 mGy, the maximum — 1.13 Gy. The analysis was performed using the DATAB and AMFIT programs (statistical software package EPICURE). A simple parametric model of excess relative risk (ERR) was used. Statistical significance and confidence intervals were obtained using the maximum likelihood method.
Results: As a result of the analysis of the solid cancer incidence risk in the EURT cohort during the 57-year follow-up period using the linear model and the 5-year latent period, a statistically significant ERR was obtained which equals to 0.052 / 100 mGy (95 % CI 0.01–0.10, p = 0.02) in the entire EURT cohort. When the group of people additionally exposed on the Techa River before the 1957 accident was excluded from the cohort, the risk became insignificant. No significant modification of the dose dependence by non-radiation factors was revealed. The obtained results are compared well with the previous studies of the exposed population in the Southern Urals which were conducted in the Urals Research Center for Radiation Medicine, as well as in the world, devoted to the study of the effects of radiation exposure on population.
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Morton, Lindsay M., Lene Veiga, Rochelle E. Curtis, Diana Withrow, Peter Inskip, Kevin C. Oeffinger, Chaya S. Moskowitz, et al. "Risk of subsequent breast cancer after radiotherapy according to hormone-receptor status: A nested case-control study in the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10520. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10520.
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10520 Background: Survivors of childhood cancer have a high absolute risk of subsequent breast cancer after chest-directed radiotherapy; however, it is not known if this risk differs by hormone-receptor status and radiation to the ovaries. Methods: We conducted a nested case-control study within the CCSS of 282 five-year survivors of childhood cancer with subsequent breast cancer and 1202 matched controls. Radiation dose to the location of the breast tumor (or corresponding location for controls) and mean dose to the ovaries were estimated from treatment records for each patient. Risk of radiation-related breast cancer was measured with the Excess Odds Ratio per Gray (EOR/Gy) and corresponding 95% confidence interval (CI), derived from conditional logistic regression. Results: The median age at subsequent breast cancer diagnosis was 39 years (range 21-58). Although 87% of cases and 70% of controls received radiotherapy, breast doses were higher in cases than controls (61% vs 24% breast dose > 10Gy), whereas ovarian doses were lower (7% vs 13% ovary dose > 5Gy). In the subset of cases (n = 159) with currently available estrogen receptor (ER) status (76% cases ER+, 24% cases ER-), there was a linear dose-response relation with radiation dose to the breast that was similar for ER+ (EOR/Gy = 0.51; 95%CI: 0.19-1.34) and ER- breast tumors (EOR/Gy = 0.41; 95%CI: 0.05-2.88). If the patient received an ovarian dose > 5Gy, this dose-response was significantly reduced for ER+ tumors but not for ER- tumors. Conclusions: Preliminary analyses demonstrate that radiation exposure to the breast to treat childhood cancer results in an increased risk of both ER+ and ER- breast cancers. The novel finding that only the risk of ER+ breast cancer is lowered if the ovaries are also exposed is consistent with known differences by hormone receptor status in the biological mechanisms of breast carcinogenesis.
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Pan, Sai Yi, Margaret de Groh, and Howard Morrison. "A Case-Control Study of Risk Factors for Salivary Gland Cancer in Canada." Journal of Cancer Epidemiology 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/4909214.
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Aim. To assess the effect of various lifestyle risk factors on the risk of salivary gland cancer in Canada using data from a population-based case-control study.Methods. Data from a population-based case-control study of 132 incident cases of salivary gland cancer and 3076 population controls were collected through self-administered questionnaire and analysed using unconditional logistic regression.Results. Four or more servings/week of processed meat product was associated with an adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) of 1.62 (1.02–2.58). Nonsignificantly increased ORs were also related to obesity, >7 drinks/week of alcohol consumption, and occupational exposure to radiation. Furthermore, nonsignificantly decreased ORs were found to be associated with high education level (>12 years) (OR=0.65), high consumption of spinach/squash (OR=0.62) and all vegetables/vegetable juices (OR=0.75), and >30 sessions/month of recreational physical activity (OR=0.78).Conclusions. This study suggests positive associations with consumption of processed meat, smoking, obesity, alcohol drinking, and occupational exposure to radiation as well as negative associations with higher education, consumption of spinach/squash, and physical activity, which suggest a role of lifestyle factors in the etiology of salivary gland cancer. However, these findings were based on small number of cases and were nonsignificant. Further larger studies are warranted to confirm our findings.
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Shkarupa, V. M., O. Yu Mishcheniuk, S. O. Henyk-Berezovska, V. O. Palamarchuk, and S. V. Klymenko. "POLYMORPHISM OF DNA REPAIR GENE XPD Lys751Gln AND CHROMOSOME ABERRATIONS IN LYMPHOCYTES OF THYROID CANCER PATIENTS EXPOSED TO IONIZING RADIATION DUE TO THE CHORNOBYL ACCIDENT." Experimental Oncology 38, no. 4 (December 22, 2016): 257–60. http://dx.doi.org/10.31768/2312-8852.2016.38(4):257-260.
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The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. Materials and Methods: XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. Results: In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04–12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. Conclusions: The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled “The Chornobyl Nuclear Accident: Thirty Years After”.
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Gurney, James G., Kirsten K. Ness, Marilyn Stovall, Suzanne Wolden, Judy A. Punyko, Joseph P. Neglia, Ann C. Mertens, Roger J. Packer, Leslie L. Robison, and Charles A. Sklar. "Final Height and Body Mass Index among Adult Survivors of Childhood Brain Cancer: Childhood Cancer Survivor Study." Journal of Clinical Endocrinology & Metabolism 88, no. 10 (October 1, 2003): 4731–39. http://dx.doi.org/10.1210/jc.2003-030784.
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Abstract The objectives of this study were 1) to compare final height and body mass index (BMI) between adult survivors of childhood brain cancer and age- and sex-matched population norms, 2) to quantify the effects of treatment- and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI of 30 kg/m2 or more (obesity). Treatment records were abstracted and surveys completed by 921 adults aged 20–45 yr who were treated for brain cancer as children and were participants in the multicenter Childhood Cancer Survivor Study. Nearly 40% of childhood brain cancer survivors were below the 10th percentile for height. The strongest risk factors for adult short stature were young age at diagnosis and radiation treatment involving the hypothalamic-pituitary axis (HPA). The multivariate odds ratio for adult short stature among those 4 yr of age or younger at diagnosis, relative to ages 10–20 yr, was 5.67 (95% confidence interval, 3.6–8.9). HPA radiation exposure increased the risk of adult short stature in a dose-response fashion (trend test, P < 0.0001). Adjuvant chemotherapy was not an independent risk factor for adult short stature. BMI distribution in survivors did not differ appreciably from that of population norms; however, in females, young age at diagnosis and HPA radiation dose (trend test, P < 0.001) were associated with risk of obesity. Except for patients treated with surgery only, survivors of childhood brain cancer are at very high risk for adult short stature, and this risk increases with radiation dose involving the HPA. We did not find a corresponding elevated risk for obesity.
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Öz, Bahadır, Serap Doğan, Ertan Emek, Muhammed Akyüz, Alper Akcan, Erdoğan Sözüer, Hızır Akyıldız, and Ergin Arslan. "Predictive Factors of Malignancy in Cytology of Indeterminate Follicular and Hürthle Cell Neoplasms of the Thyroid Gland." International Surgery 103, no. 1-2 (April 1, 2019): 9–14. http://dx.doi.org/10.9738/intsurg-d-15-00187.1.
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The objective of the current study was to determine the risk of malignancy in patients with thyroid nodules with cytology of indeterminate follicular and indeterminate Hürthle cell neoplasm (HN). The cytologic diagnosis of follicular neoplasm (FN) or HN remains a diagnostic challenge. Often, surgery is recommended for such lesions. A retrospective analysis was performed on 80 patients who underwent thyroid surgery following a diagnosis of indeterminate FN and indeterminate HN in thyroid fine-needle aspiration biopsy. Sex; age; family history of thyroid cancer and radiation exposure; coexisting thyroid conditions, such as solitary nodule; multinodularity; cytologic diagnosis; sonographic features; type of surgical treatment; and histopathologic results were recorded. Of the 80 patients, 52 (65%) had FN on fine-needle aspiration biopsy cytology and 28 (35%) had HN. A total of 23 patients (28.7%) had primary thyroid cancers on surgical pathology, and 57 (71.3%) had benign diagnoses. Univariate analysis showed no differences between the benign and malignant groups by sex, nodule size, family history of thyroid cancer, history of radiation exposure, presence of solitary nodule or multinodularity in the nodular features. In multivariate binary logistic regression analysis, the factors that were statistically significant predictors of malignancy were microcalcification [odds ratio (OR), 10.9; 95% confidence interval (CI), 2.18–54.7; P = 0.004], being older than 45 years (OR, 4.2; 95% CI, 1.25–14.63; P = 0.02]. The independent predictors of malignancy in FN and HN are micorcalcification and being older than 45 years, the use of which may predict the risk of thyroid cancer.
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Endo, Mayumi, Jessica B. Liu, Marcelle Dougan, and Jennifer S. Lee. "Incidence of Second Malignancy in Patients with Papillary Thyroid Cancer from Surveillance, Epidemiology, and End Results 13 Dataset." Journal of Thyroid Research 2018 (June 26, 2018): 1–11. http://dx.doi.org/10.1155/2018/8765369.
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Increased risk of second primary malignancy (SPM) in papillary thyroid cancer (PTC) has been reported. Here, we present the most updated incidence rates of second primary malignancy from original diagnosis of PTC by using the data from the Surveillance, Epidemiology, and End Results. In this cohort, 3,200 patients developed SPM, a substantially higher number than in the reference population of 2,749 with observed to expected ratio (O/E) of 1.16 (95% CI; 1.12–1.21). Bone and joint cancer had the highest O/E ratio of 4.26 (95% confidence interval [CI] 2.33–7.15) followed by salivary gland (O/E 4.15; 95% CI 2.76–6.0) and acute lymphocytic leukemia (O/E 3.98; 95% CI 2.12–6.8). Mean age at the diagnosis of SPM was 64.4 years old. Interestingly, incidence of colorectal cancer was lower in thyroid cancer survivors compared to general population (large intestine O/E 0.3; 95% CI 0.06–0.88, rectum O/E 0.6; 95% CI 0.41–0.85); however, this was not observed in patients who underwent radiation therapy. The incidence of SPM at all sites was higher during 2000–2012 compared to 1992–1999 (O/E 1.24 versus 1.10). Surprisingly, patients with micropapillary cancer had higher incidence of SPM than counterparts with a larger tumor in radiation group (O/E of 1.40 versus 1.15). O/E of all cancers were higher in males compared to females with O/E of 1.41 versus 1.17 during the period of 2000–2012. Diagnosis of PTC before age 50, especially at age 30–34, was associated with higher incidence of overall SPM (age 30–34; O/E 1.43; 95% CI; 1.19–1.71). Efficient monitoring strategies that include age at the time of thyroid cancer diagnosis, exposure to radiation, gender, and genetic susceptibility may successfully detect SPM earlier in the disease course. This is especially important given the excellent prognosis of the initial thyroid cancer itself.
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Hafez, Navid, Rong Wang, Michael E. Hurwitz, Xiaomei Ma, and Daniel Peter Petrylak. "The impact of androgen deprivation and pelvic radiation on the development of bladder cancer." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 439. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.439.
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439 Background: The male predilection of urothelial bladder cancer (UBC) as well as the expression of the androgen receptor in bladder tissue point to the role for androgens in UBC tumorigenesis. Animal studies demonstrate a potential role for androgen deprivation in diminishing UBC. More recently, two separate groups demonstrated decreased rates of both primary and recurrent UBC in prostate cancer patients previously receiving androgen deprivation therapy (ADT). Given the common use of radiation therapy (RT) in the treatment of localized prostate cancer, and previous data supporting the increased frequency of UBC in prostate cancer patients treated with RT, the interaction between ADT and RT in UBC remains an important consideration. Methods: Using the linked SEER-Medicare database, we investigated the interactions among ADT, RT and UBC by performing a retrospective cohort study of elderly (age 66-99) prostate cancer patients diagnosed between 1999-2011. Kaplan-Meier analysis and Cox proportional modeling were used to determine the risk of developing secondary bladder cancer after prostate cancer treatment (based on exposure to ADT, RT, both, or neither). All analyses were two-sided. Results: Of 121,927 patients with primary prostate cancer, 1,466 (1.20%) developed subsequent UBC with a median follow up of 5.08 years (range 0.003-12.00). Compared with patients never receiving ADT or RT (n = 43,809), the hazard ratios for the development of secondary bladder cancer in patients ever receiving ADT but no RT (n = 14,009), RT but no ADT (n = 16,672), or both ADT and RT (n = 17,465) were 0.76 (95% confidence interval [CI]: 0.63-0.91 ), 0.73 (95% CI: 0.64-0.83), and 0.69 (95% CI: 0.61-0.79), respectively. Conclusions: Both ADT and RT are independently associated with a reduced risk of secondary bladder cancers in prostate cancer patients. The finding of decreased UBC incidence in patients receiving RT was surprising, and in direct contradiction to previous studies of similar patient populations. Possible explanations include differences in cohort selection, changes in RT delivery, and differences in control groups.
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Bashore, Lisa, Zahra Merchant, Philip Lupo, Allison A. King, Tyler Hamby, Deokumar Srivastava, Rebecca M. Howell, et al. "Educational attainment in long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 10063. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.10063.
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10063 Background: Diagnosis and treatment of childhood cancer place survivors at risk for lower educational attainment, the increased burden of chronic conditions on attainment has not been examined. Methods: Participants included 16724 survivors (48% female; mean diagnosis age 9.1 years, current age 36.2 years, time since diagnosis 26.6 years) and 4098 siblings (mean current age 39.3 years) Educational attainment was categorized as college graduation (yes/no) among survivors ≥ age 25 years. Chronic conditions occurring before age 25 years of age were graded using Common Terminology for Adverse Events 4.3. Modified Poisson regression models estimated relative risks (RR) and 95% confidence intervals (CI) of treatment exposures and chronic conditions on education attainment, adjusting for age at diagnosis and sex. Results: College graduation was reported by 8391 (51%) survivors and 2410 (59%) siblings. Survivors of all diagnoses were more likely to not graduate compared to siblings (all p’s < 0.05), with survivors of CNS tumor (RR1.36, CI 1.25-1.49), leukemia (RR 1.17, CI 1.07-1.28), and Hodgkin lymphoma (RR 1.17, CI 1.07-1.29) being at higher risk than survivors of neuroblastoma. Compared to survivors with no history of cranial radiation therapy (CRT), higher risk of not graduating college was seen in those who received 20-30Gy (RR 1.16, CI 1.09-1.25), 30-50Gy (RR 1.37, CI 1.26-1.49) and ≥50Gy (RR 1.35, CI 1.28-1.42). Among survivors not exposed to CRT, dexamethasone had a protective effect on college education (RR 0.88, CI 0.80-0.97) compared to no corticosteroid exposure. Male sex and older age (≥ 5 years) at diagnosis were associated with being more likely to not graduate college. survivors reporting any serious/life threatening chronic condition prior to age 25 years (grades 3-4) were more likely to not graduate college (RR 1.14, 95% CI 1.10-1.18) compared to no or mild/moderate conditions (grades < 3). Conclusions: Survivors reporting chronic conditions are less likely to complete a college education by age 25 years and may need additional early educational or vocational resources.
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Castellino, Sharon M., Ann M. Geiger, Ann C. Mertens, Wendy M. Leisenring, Janet A. Tooze, Pam Goodman, Marilyn Stovall, Leslie L. Robison, and Melissa M. Hudson. "Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study." Blood 117, no. 6 (February 10, 2011): 1806–16. http://dx.doi.org/10.1182/blood-2010-04-278796.
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Abstract The contribution of specific cancer therapies, comorbid medical conditions, and host factors to mortality risk after pediatric Hodgkin lymphoma (HL) is unclear. We assessed leading morbidities, overall and cause-specific mortality, and mortality risks among 2742 survivors of HL in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study of survivors diagnosed from 1970 to 1986. Excess absolute risk for leading causes of death and cumulative incidence and standardized incidence ratios of key medical morbidities were calculated. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of risks for overall and cause-specific mortality. Substantial excess absolute risk of mortality per 10 000 person-years was identified: overall 95.5; death due to HL 38.3, second malignant neoplasms 23.9, and cardiovascular disease 13.1. Risks for overall mortality included radiation dose ≥ 3000 rad ( ≥ 30 Gy; supra-diaphragm: HR, 3.8; 95% CI, 1.1-12.6; infradiaphragm + supradiaphragm: HR, 7.8; 95% CI, 2.4-25.1), exposure to anthracycline (HR, 2.6; 95% CI, 1.6-4.3) or alkylating agents (HR, 1.7; 95% CI, 1.2-2.5), non–breast second malignant neoplasm (HR, 2.6; 95% CI 1.4-5.1), or a serious cardiovascular condition (HR, 4.4; 95% CI 2.7-7.3). Excess mortality from second neoplasms and cardiovascular disease vary by sex and persist > 20 years of follow-up in childhood HL survivors.
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Morton, Lindsay M., Danielle M. Karyadi, Steven Hartley, Megan Frone, Joshua N. Sampson, Rebecca M. Howell, Joseph Philip Neglia, et al. "Subsequent neoplasm risk associated with rare variants in DNA repair and clinical radiation sensitivity syndrome genes: A report from the Childhood Cancer Survivor Study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 10028. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.10028.
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10028 Background: Radiotherapy for childhood cancer is associated with strikingly elevated risk for developing subsequent neoplasms (SNs). Whether mutations in DNA repair and radiation sensitivity genes modulate SN risks is largely unknown. Methods: We conducted whole-exome sequencing in 5105 long-term childhood cancer survivors of European descent (mean follow-up = 32.7 years). SnpEff and ClinVar identified potentially damaging rare variants in 476 DNA repair or radiation sensitivity genes. Conditional logistic regression assessed SN risk associated with these variants aggregated by gene or pathway (N = 155 with ≥5 carriers). Controls were matched on sex, childhood cancer type and diagnosis age, radiation dose to the SN site, and survival. Exact p-values were calculated by permutation. Analyses used all survivors or subsets stratified on radiation dose. Results: A total of 1108 (21.7%) survivors developed at least one SN type known to be related to ionizing radiation exposure (e.g., breast cancer, basal cell carcinoma, meningioma, thyroid cancer, sarcoma). Radiation-related SN risk was associated with homologous recombination (HR) gene variants for SN sites that received > 0- < 10 Gy (20.9% cases, 11.0% controls; odds ratio [OR] = 2.20, 95% confidence interval [CI] 1.52-3.18; P = 1.41x10-4), most notably for FANCM (3.1% cases, 0.5% controls; OR = 9.91, 95%CI 3.73-26.4; P = 2.85x10-4). For radiation-related SNs at sites with higher doses (≥10 Gy), associations were not observed for the HR pathway (14.4% cases, 12.4% controls, P = 0.17) but were observed for two individual genes implicated in double-strand DNA break repair, EXO1 (1.8% cases, 0.4% controls; OR = 6.50, 95%CI 3.49-12.1; P = 7.43x10-4) and NEIL3 (0% cases, 1.0% controls; P = 3.23x10-4). Conclusions: In this discovery study, we identified dose-specific novel associations between SN risk after radiotherapy for childhood cancer and potentially damaging rare variants in genes involved in double-strand DNA break repair, particularly HR. If replicated, these results could impact long-term screening of childhood cancer survivors and risk-benefit assessments of treatment approaches.
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Castillo, Jorge J., Ilya Glezerman, Susan Boklage, Joseph Chiodo, and Kathy L. Schulman. "Incidence of hyponatremia in a cohort of patients with colorectal cancer." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 545. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.545.
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545 Background: Hyponatremia (HN), a common electrolyte disturbance in hospitalized patients, is a prognostic factor in some cancers. The incidence of HN in patients diagnosed with colorectal cancer (CRC) is unknown and is investigated here. Methods: This retrospective cohort analysis combined electronic medical record and tumor registry data from an integrated delivery network. Patients included were adults diagnosed with incident invasive CRC between 2005 and 2011 with ≥1 administration of radiation or chemotherapy within 6 months of diagnosis who met continuous clinical activity criteria. Exclusions included unknown index cancer stage or ≥1 post-index hypovolemic HN episode. Patients were followed until study end, death, clinical trial entry, new primary cancer onset, or end of continuous clinical activity. HN incidence (serum sodium ≤135 mEq/L) was measured per 1,000 person years (PY) of observation (95% confidence intervals [CI]) and classified as mild (131–135), moderate (125–130) or severe (<125) based on the lowest observed value. Results: In all, 132 CRC patients were included (52% male; mean [SD] age 64±13.1 years, 99% Caucasian). Mean (SD) follow-up was 3±2.6 years. Thirty-six percent of patients had metastatic disease at diagnosis and 80% received chemotherapy, 39% radiation therapy and 83% surgical resection. Patients with HN post-CRC diagnosis had significantly greater incidence of metastatic disease during follow-up (p=0.033) and exposure to anti-metabolites (p=0.023) or platinum based agents (p=0.017). Episodes of HN (n=262) occurred in 81 patients (61%) at a rate of 598 per 1,000 PY (95% CI, 523–680). Mean (SD) episodes per patient were 1.8±2.6. Overall, 84% of episodes were mild, 14% moderate and 2% severe; 52% were classified as syndrome of inappropriate antidiuretic hormone secretion. Mean (SD) time to first hyponatremia episode was 139±296 days, with a median duration of 12 days; 84% of patients had a first episode within the first 6 months. Conclusions: The incidence of HN after diagnosis with CRC was about 61% and episodes occurred primarily within 6 months of diagnosis. Based on these results, along with emergent evidence from other studies, clinicians should anticipate HN in newly-diagnosed CRC patients.
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Wendel, Courtney L., Jon A. Anderson, Timothy J. Blackburn, and Charles T. Quinn. "Burden of Medical Radiation Exposure in Children with Sickle Cell Disease." Blood 114, no. 22 (November 20, 2009): 1525. http://dx.doi.org/10.1182/blood.v114.22.1525.1525.
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Abstract Abstract 1525 Poster Board I-548 BACKGROUND Children with sickle cell disease (SCD) present to medical attention repeatedly throughout childhood for medical complications. Chest radiographs are often obtained for fever and respiratory symptoms, and plain radiographs are often ordered because of bone pain. Computed tomography (CT) and nuclear medicine (NM) studies may also be obtained for other complications. Exposure to medical radiation may increase the risk of cancer, especially in children. Growing children are inherently radiosensitive because of their high proportion of dividing cells, and children have more remaining years of life than adults during which cancer can develop. Therefore, it is important to determine the magnitude of medical radiation exposure in children with SCD because they could be so frequently exposed. METHODS We reviewed the medical records for all members of the Dallas Newborn Cohort (Blood 2004;103:4023-7) to determine the number and type of radiographic studies each individual received from 1996 to the present. We recorded the type of radiographic study, body location, clinical indication, date of study, age at the time of study, and the number and types of views when applicable. We also recorded slice thickness and mode for CT scans as well as injection activity, radionuclide, and type of radiopharmaceutical for nuclear medicine studies. To account for different lengths of follow-up, we standardized the number of radiographic studies to yearly rates for each individual to determine the projected number of studies a SCD patient would receive by 18 years of age. RESULTS We studied 938 patients (52.8% male) with a mean follow-up of 9.4 years (median 9.2, range 0.1 – 20.6). 571 had sickle cell anemia (SS), 283 had sickle-hemoglobin C disease (SC), 63 had Sβ+-thalassemia (Sβ+), and 21 had Sβ0-thalassemia (Sβ0). We identified 9,246 radiographic studies, including 8,697 radiographs, 441 CT scans, and 108 NM studies. 711 (76%) patients had at least one radiographic study. Patients with SS or Sβ0 were more likely to have had at least one radiographic study than those with SC or Sβ+ (77% vs. 65%; P<0.0001). The mean number of studies per patient was 9.9 [95% confidence interval (C.I.) 8.9 – 10.9; range 0 – 115], corresponding to a mean rate of 1.5 per year (95% C.I. 1.3 – 1.6; range 0 – 27.3). We project that a patient with SCD will be exposed to the radiation from 26.7 (95% C.I. 24.1 – 29.3; range 0 – 492.1) radiographic studies by 18 years of age. Approximately 5% of patients with SCD will be exposed to 100 or more radiographic studies during childhood. CONCLUSIONS Children with SCD are frequently exposed to medical radiation. Some are exposed to over 100 radiographic studies. Radiographs of the painful part are frequently obtained but are infrequently indicated. Because growing children are more radiosensitive than adults and have more remaining years of life, medical radiation exposure could be clinically significant. We are now calculating the radiation effective doses for this cohort to quantify the risk of malignancy. It is prudent to limit the medical radiation exposure of this high-risk population. Disclosures No relevant conflicts of interest to declare.
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Abrahao, Renata, Ann M. Brunson, Justine M. Kahn, Qian Li, Aaron S. Rosenberg, Ted Wun, and Theresa Keegan. "Second Primary Malignancy Risk Among HIV-Uninfected and HIV-Infected Survivors of Hodgkin Lymphoma: A 30-Year Follow-up Population-Based Study." Blood 136, Supplement 1 (November 5, 2020): 15–17. http://dx.doi.org/10.1182/blood-2020-137728.
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Introduction Second primary malignancy (SPM) is one of the most devastating late complications following Hodgkin lymphoma (HL) treatment. Historically, the most common SPMs in patients treated for HL are solid tumors, which are largely related to radiation exposure during initial therapy. For the last three decades, efforts to address the risk of SPM after HL therapy have focused on reducing exposure to radiation, as well as refining the approach for patients where radiation is indicated. To date, few population-based studies in the United States have quantified the burden of SPMs and evaluated the potential effect of changes in therapeutic management over time. Additionally, to our knowledge, no study has compared SPM risk between human immunodeficiency virus (HIV)-infected and HIV-uninfected HL survivors. Methods We used data from the California Cancer Registry on 21,043 patients diagnosed with primary HL between 1988 and 2015 with follow-up through 2017. We calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) and absolute excess risks (AERs) to compare SPM incidence in our HL cohort with the expected number of first primary cancer incidence in the general California population, based on patient's age at diagnosis (5-year categories), sex, calendar year (3-year intervals), cancer site, and race/ethnicity. SIRs are presented by HIV status, SPM latency, treatment era, and cancer type. P-values for trends were used to examine whether SPM risk changed over time. Findings Among 20,303 HIV-uninfected patients (median follow-up of 14.1 years), overall SPM risk was increased 1.95-fold compared with the general population (SIR=1.95, 95% CI 1.86-2.04). In 740 HIV-infected patients (median follow-up of 11.7 years), overall risk was increased 2.68-fold compared with the general population (SIR=2.68, 95% CI 2.0-3.40), translating to an 37% higher incidence of SPM in HIV-infected vs. HIV-uninfected patients. The AER (per 10,000 person-years) of SPM was 43.1 in HIV-uninfected and 76.5 in HIV-infected patients, resulting in a 33.4 excess SPM per 10,000 person-years in HL survivors with HIV. Malignancies that contributed the most to overall AER were non-Hodgkin lymphoma (NHL), female breast and lung cancers in HIV-uninfected patients; and Kaposi sarcoma, NHL, anorectal and head & neck (HNC) cancers in HIV-infected patients. Notably, among HIV-uninfected patients, the highest overall risk of SPM occurred ≥20 years after diagnosis (SIR= 2.27, 95% CI 1.99-2.58) (Figure). In contrast, the highest overall risk in HIV-infected patients was observed <2 years after diagnosis (SIR=4.42, 95% CI 2.53-7.19). Radiation used decreased from 46.9% in 1988-1996 to 29.5% in 2007-2015. Among HIV-uninfected patients, there was a trend towards decreased risk over time of overall and selected solid SPMs (lung, female breast, and gastrointestinal cancers) (Table). In an analysis restricted to HIV-uninfected patients who received radiation irrespective of chemotherapy, findings also suggested a declined risk of overall and selected solid SPMs over time: any solid (SIR=2.15 in 1988-1996 and SIR=1.30 in 2007-2015, p<0.0001), lung (SIR=3.69 in 1988-1996 and SIR=1.81 in 2007-2015, p=0.0031), and female breast (SIR=2.95 in 1988-1996 and SIR=0.63 in 2007-2015, p<0.0001). Conclusion Compared with the general population, the risk of developing a SPM following HL treatment was significantly higher among both HIV-uninfected and HIV-infected patients, with the absolute excess risk greater for those with HIV infection. There were different temporal patterns and types of SPM between HIV-uninfected and HIV-infected patients. These findings prompt the question on whether earlier and/or more intensive cancer screening should be pursued for HIV-infected survivors. The trend towards decreased risk for selected solid SPMs among HIV-uninfected patients, especially lung and female breast cancers, suggest that strategies to reduce radiation in HL survivors may be working. Despite promising trends in this group, the observation that SPM risk was highest ≥20 years after initial therapy further highlights the need for long-term surveillance and survivorship care in this at-risk population. Disclosures Rosenberg: Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Wun:Glycomimetics, Inc.: Consultancy.
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Zaorsky, Nicholas George, Theresa Maria Malatesta, Robert Benjamin Den, Evan John Wuthrick, Maria Werner-Wasik, Wenyin Shi, Peter H. Ahn, et al. "Assessing the value of an optional radiation oncology clinical rotation during the core clerkships in medical school." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19507-e19507. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19507.
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e19507 Background: Few medical students are given proper clinical training in oncology, much less radiation oncology. We evaluate the value of adding a radiation oncology clinical rotation to the medical school curriculum. Methods: In July 2010, Jefferson Medical College offered a 3-week radiation oncology elective rotation for third-year medical students during the core surgical clerkship. During 2010-2012, 52 students chose to enroll in this rotation. The rotation included outpatient clinics, inpatient consults, didactic sessions, and case-based presentations by the students. Tests of students’ knowledge of radiation oncology were administered anonymously before and after the rotation to evaluate the educational effectiveness of the rotation. Students and radiation oncology faculty were given surveys to assess feedback about the rotation. Results: The students’ pre-rotation test scores had an average of 64% (95% confidence interval [CI]: 61%, 66%), which improved after the rotation to 82% (95% CI: 80%, 83%; 18% absolute improvement). In exam question analysis, scores improved in clinical oncology from 63% to 79%, in radiobiology from 70% to 77%, and in medical physics from 62% to 88%. Improvements in all sections but radiobiology were statistically significant. Students rated the usefulness of the rotation as 8.1 (scale 1-9, 95% CI: 7.3, 9.0), their understanding of radiation oncology as a result of the rotation as 8.8 (95% CI: 8.5, 9.1), and their recommendation of the rotation to a classmate as 8.2 (95% CI: 7.6, 9.0). Radiation oncology faculty rated their belief that this rotation would be valuable to students as 8.2 (scale 1-9), that students had appropriate responsibilities in the clinic as 7.9, and that the lectures and meetings that students attended were at an appropriate level as 8.1. Conclusions: Integrating a radiation oncology clinical rotation into the medical school curriculum improves student knowledge of radiation oncology, including aspects of clinical oncology, radiobiology, and medical physics. The rotation is appreciated by both students and faculty. We recommend including exposure to radiation oncology as part of the core clinical curriculum for all medical students.
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Daly, Corinne, David Urbach, Therese A. Stukel, Wayne Deitel, Paul C. Nathan, Lawrence Frank Paszat, and Nancy N. Baxter. "Rates of diagnostic imaging in long-term survivors of young adult malignancies." Journal of Clinical Oncology 30, no. 34_suppl (December 1, 2012): 69. http://dx.doi.org/10.1200/jco.2012.30.34_suppl.69.
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69 Background: In general, clinical practice guidelines do not recommend the use of diagnostic imaging in long-term surveillance of cancer survivors. Although warranted diagnostic imaging has clinical benefits, the overuse of imaging in cancer survivors may lead to false-positive results, more invasive tests, economic burden and unnecessary radiation exposure. The objective of this study was to determine rates of diagnostic imaging in long-term young adult cancer survivors (YAS) compared to cancer-free controls in Ontario, Canada. Methods: We conducted a population-based retrospective study. Young adults aged 20 to 44 diagnosed with an invasive malignancy between 1992 and 1999 who lived at least 5 years without recurrent disease were identified in the Ontario Cancer Registry. YAS were matched 1:5 to randomly selected cancer-free controls on calendar year of birth, sex, and place of residence. The rate at which YAS received plain radiography, CT, ultrasound and nuclear medicine studies was compared to rates received by controls using Poisson regression. Results: 20,911 survivors and 104,524 controls met our inclusion criteria. YAS received all types of diagnostic imaging at significantly higher rates than controls in the 10 year period after 5-year recurrence-free survival. YAS received CT scanning at a rate 3.6-fold higher than controls (95% confidence interval [CI]: 3.37, 3.62). In contract, the difference in rates of ultrasound between the two groups was more modest (rate ratio [RR] = 1.40, 95% CI: 1.38, 1.43). YAS also received plain radiography (RR =1.66, 95% CI: 1.64, 1.69) and nuclear studies (RR=1.97, 95% CI: 1.89, 2.04) at significantly higher rates than controls, resulting in a 4.6-fold adjusted higher diagnostic radiation dose than controls. Conclusions: Survivors received significantly higher rates of all diagnostic studies after 5-year survival compared to their age-matched cancer-free counterparts. Hazards associated with overuse of imaging such as radiation exposure and heightened anxiety about test results need to be considered. Both patients and providers should be educated about the role of diagnostic imaging in long-term surveillance including the utility of studies without radiation, such as ultrasound.
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Elsworthy, M., and P. N. Plowman. "Peripheral blood lymphocyte counts during standard conformal radiotherapy and TomoTherapy/IMRT for prostate cancer." Journal of Radiotherapy in Practice 7, no. 4 (December 2008): 223–27. http://dx.doi.org/10.1017/s1460396908006444.
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AbstractLymphopaenia is the earliest and the most sensitive routinely assessed biological parameter of corporeal radiation exposure in clinical practice; bone marrow, lymph nodes and peripheral blood lymphocyte populations are also at risk. During radical prostate radiotherapy, in 28 patients, the mean peripheral lymphocyte count fell from 1.76 × 109/l (standard deviation (SD) 0.63, 95% confidence interval (conf.) 0.23) to 1.10 × 109/l (SD 0.38, conf. 0.14), (p < 0.05). The question was asked as to whether intensity-modulated radiation therapy (IMRT) by TomoTherapy would cause more lymphopaenia than three-field conformal radiotherapy, bearing in mind the ‘low dose bath’ effect of IMRT and the long ‘beam-on’ times. Thirteen patients receiving three-field conformal radiotherapy experienced a fall in peripheral lymphocyte counts from 2.02 (SD: 0.62. conf. 0.43) to 1.17 × 109/l (SD: 0.47, conf. 0.26) after 34–38 Gy, as compared to a fall from 1.6 × 109/l (SD: 0.6, conf. 0.35) to 1.04 × 109/l (SD: 0.3, conf. 0.15) for 15 TomoTherapy patients—non-significant differences. We conclude that for this (approximately) standard, small-volume pelvic radiotherapy and to the dose under scrutiny, we cannot detect differences between the two radiotherapy techniques in terms of the lymphopaenia accruing. Neutrophil counts were similarly non-significantly different.
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Friedman, Danielle Novetsky, Suzanne L. Wolden, Zoltan Antal, Chaya S. Moskowitz, Patrick Hilden, Nai-Kong V. Cheung, Brian H. Kushner, et al. "Insulin and glucose homeostasis in childhood cancer survivors treated with abdominal radiation: A pilot study." Journal of Clinical Oncology 34, no. 3_suppl (January 20, 2016): 108. http://dx.doi.org/10.1200/jco.2016.34.3_suppl.108.
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108 Background: Previous reports have suggested an increased risk of Type I and Type II diabetes mellitus (DM) in childhood cancer survivors exposed to abdominal radiotherapy (RT). The mechanisms leading to DM in this population, however, remain unknown. We sought to clarify the pathophysiology leading to these derangements by performing dynamic testing of glucose and insulin in survivors previously treated with abdominal RT. Methods: Cross-sectional pilot study of 2-year survivors of childhood cancer treated with abdominal RT at Memorial Sloan Kettering between 1975 – 2009. Eligible participants were < 21 years of age at exposure to abdominal RT; those with a known diagnosis of DM or prior exposure to brain or total body RT were excluded. Survivors underwent formal 2-hour glucose tolerance testing; auto-antibodies (insulin auto-antibodies, islet cell autoantibody, glutamic acid decarboxylase) typically present in patients with Type I DM and hemoglobin A1c levels were assessed. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda index. Results: 21 survivors were enrolled (male: 47.6%; median age at RT: 3.3 years; median age at study: 14.4 years [range: 8.3 – 46.9]; median time from abdominal RT: 10.7 years). Primary diagnoses included neuroblastoma (n = 15), rhabdomyosarcoma (n = 3), Wilms (n = 1), Hodgkin lymphoma (n = 1), rhabdoid tumor (n = 1). None of the participants were obese (body mass index [BMI] range: 14.7 – 23.2 kg/m2). Five participants (23.8%, 95% confidence interval: 8% – 47%) had glucose derangements at a median of 8.4 years after RT (one with impaired fasting glucose [fasting glucose ≥ 100 mg/dl) and four with impaired glucose tolerance [2-hour glucose 140-199 mg/dl]). Two additional participants with normal glucose tolerance had impaired insulin sensitivity based on an abnormal Matsuda Index and HOMA-IR. None of the participants had abnormal autoantibodies, insulinopenia, or hemoglobin A1c levels. Conclusions: These findings suggest that nonobese childhood cancer survivors treated with abdominal RT may be at high-risk for subclinical derangements of glucose and insulin. Further study is warranted in larger survivor cohorts. Clinical trial information: NCT02248779.
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Sakaki, Junichi R., Melissa M. Melough, Mary B. Roberts, Charles B. Eaton, Aladdin H. Shadyab, Abrar A. Qureshi, Ock K. Chun, and Eunyoung Cho. "Citrus Consumption and the Risk of Non-Melanoma Skin Cancer in the Women’s Health Initiative." Cancers 13, no. 9 (April 30, 2021): 2173. http://dx.doi.org/10.3390/cancers13092173.
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Evidence from animal studies suggests that furocoumarins, compounds present in citrus products, can increase the risk of non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. The objective of this study was to determine the relationship between citrus intake and NMSC risk among postmenopausal women from the Women’s Health Initiative (WHI) Observational Study, who were aged 50–79 years at enrollment (1993–1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (p-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. In conclusion, there were indications of a slightly higher risk of incident NMSC among citrus juice consumers; however, further longitudinal and mechanistic studies are needed to confirm the key risk factors.
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Gong, Jingyi, David Payne, Jesse Pittard Caron, Camden Bay, Bradley Alexander McGregor, Jon Hainer, Ann H. Partridge, et al. "Cardiorespiratory fitness and cardiovascular mortality after prolonged androgen deprivation therapy for prostate cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 11576. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.11576.
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11576 Background: Androgen deprivation therapy (ADT) plays a pivotal role in management of prostate cancer (PC), with prolonged ADT favored over short-term use in the definitive treatment of high risk PC with radiation. Objectives: To compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure, and to explore how duration of ADT exposure influences CRF and CV mortality risk. Methods: This is a retrospective study of patients referred for exercise treadmill testing (ETT) after a diagnosis of PC. PC risk classification was based on Gleason score (GS) at diagnosis: high risk GS ≥ 8, intermediate risk GS= 7, and low risk GS ≤ 6. CRF was categorized according to metabolic equivalents (METs): METs ≥ 8 defined as good CRF and METs < 8 as reduced CRF. ADT exposure was grouped as short-term (≤ 6 months) versus prolonged (> 6 months). Results: 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0-7.9) after diagnosis of PC. 150 patients (24.3%) received ADT prior to ETT; 51 with short-term versus 99 with prolonged exposure. 524 (85.1%) patients had ≥ 2 CV risk factors, and 28 CV deaths occurred over 4.2 (interquartile range: 2.3-7.1) years following the ETT. Reduced CRF was more frequent among ADT-exposed versus ADT-naive patients (48.7 versus 32.6%, p< 0.001). Prolonged ADT was associated with reduced CRF (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.31-5.61; p=0.007) and increased CV mortality (hazard ratio (HR): 3.87; 95% CI: 1.16-12.96; p=0.03) in adjusted analyses. In contrast, short-term ADT exposure was not independently associated with either reduced CRF (OR 1.71; 95% CI: 1.00-2.94); p=0.05) or CV mortality (HR: 1.60; 95% CI: 0.51-5.01; p=0.42). Conclusions: Among patients with PC and high baseline CV risk, > 6 months ADT exposure but not less was associated with reduced CRF and increased CV mortality. Reduced CRF may in part mediate increased CV mortality risk. Exercise interventions concurrent with prolonged ADT warrants investigation to potentially offset risk.
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Foster, Kayla L., Daniel M. Green, Sedigheh Mirzaei Salehabadi, Mengqi Xing, Kirsten K. Ness, Kevin R. Krull, Tara M. Brinkman, et al. "Late health outcomes in survivors of Wilms tumor: A report from the St. Jude Lifetime (SJLIFE) cohort study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10038. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10038.
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10038 Background: We aimed to characterize late health, neurocognitive, and physical performance outcomes among survivors of Wilms tumor. Methods: Wilms tumor survivors (n = 280), ≥ 5 years from diagnosis, participating in SJLIFE were clinically assessed along with a community control sample (n = 625). Health outcomes were graded per a modified Common Terminology Criteria for Adverse Events (grade 1 [mild] to grade 4 [life threatening]). Standardized neurocognitive testing was graded using age-adjusted z-scores. Aerobic function (six-minute walk), mobility (timed up and go) and flexibility (sit and reach) were assessed. Associations between treatment exposures and prevalent conditions were examined by multivariable logistic regression, adjusted for current age, sex and race. Results: Survivors (59% female, 73% white), median age 3 years (range 0-15) at diagnosis and 31 years (9-58) at evaluation, were comprehensively evaluated on the St. Jude campus. Two-thirds (67%) were treated with doxorubicin (median dose 175 mg/m2 range 52-490), 167 (60%) received abdominal radiation (median dose 12 Gy range 8.8-61.2) and 25% received chest radiation (12 Gy range 9-44). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI 6.7-8.2) grade 2-4 conditions, compared to 4.2 (CI 3.9-4.6) and 2.3 (CI 2.1-2.5), respectively, among controls. The most prevalent medical conditions (grade ≥ 2) are reported in the table. Abnormal glucose metabolism was associated with abdominal radiation (relative risk [RR] 5.1 CI 1.4-19.0); restrictive pulmonary defects with chest radiation (RR 24.0 CI 3.2-180); and cardiomyopathy (RR 15.6 CI 1.9-128), pulmonary diffusion (RR 4.5 CI 1.3-15.1), and chronic kidney disease (RR 4.5 CI 1.3-16.1) with doxorubicin exposure. Survivors had a three-fold higher risk (standardized incidence ratio 3.5, CI 2.2-6.6) for subsequent neoplasms. Impairments (grade ≥ 2) in executive function (20% vs. 12%), attention (17% vs. 9%), memory (21% vs. 10%), and processing speed (20% vs. 8%) were more frequent in survivors than controls (p < 0.05). Impairments in aerobic function (13.6%), mobility (13.6%), and flexibility (11.1%) were higher than expected (p < 0.01). Significant associations were not identified between treatment exposures and neurocognitive or physical performance outcomes. Conclusions: Systematic clinical assessment identified a significant burden of chronic health conditions and previously unrecognized neurocognitive and physical performance limitations in survivors of Wilms tumor.[Table: see text]
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Buja, Alessandra, John H. Lange, Egle Perissinotto, Giuseppe Rausa, Francesco Grigoletto, Cristina Canova, and Giuseppe Mastrangelo. "Cancer incidence among male military and civil pilots and flight attendants: an analysis on published data." Toxicology and Industrial Health 21, no. 9 (October 2005): 273–82. http://dx.doi.org/10.1191/0748233705th238oa.
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Flight personnel are exposed to cosmic ionizing radiation, chemicals (fuel, jet engine exhausts, cabin air pollutants), electromagnetic fields from cockpit instruments, and disrupted sleep patterns. Only recently has cancer risk among these workers been investigated. With the aim of increasing the precision of risk estimates of cancer incidence, follow-up studies reporting a standardized incidence ratio for cancer among male flight attendants, civil and military pilots were obtained from online databases and analysed. A meta-analysis was performed by applying a random effect model, obtaining a meta-standardized incidence ratio (SIR), and 95% confidence interval (CI). In male cabin attendants, and civil and military pilots, meta-SIRs were 3.42 (CI=1.94-6.06), 2.18 (1.69-2.80), 1.43 (1.09-1.87) for melanoma; and 7.46 (3.52-15.89), 1.88 (1.23-2.88), 1.80 (1.25-2.58) for other skin cancer, respectively. These tumors share as risk factors, ionizing radiation, recreational sun exposure and socioeconomic status. The meta-SIRs are not adjusted for confounding; the magnitude of risk for melanoma decreased when we corrected for socioeconomic status. In civil pilots, meta-SIR was 1.47 (1.06-2.05) for prostate cancer. Age (civil pilots are older than military pilots and cabin attendants) and disrupted sleep pattern (entailing hyposecretion of melatonin, which has been reported to suppress proliferative effects of androgen on prostate cancer cells) might be involved. In male cabin attendants, meta-SIR was 21.5 (2.25-205.8) for Kaposi’s sarcoma and 2.49 (1.03-6.03) for non-Hodgkin’s lymphoma. AIDS, which was the most frequent single cause of death in this occupational category, likely explains the excess of the latter two tumors.
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Brinkman, Tara M., Wei Liu, Gregory T. Armstrong, Amar J. Gajjar, Thomas E. Merchant, Cara I. Kimberg, Larry E. Kun, et al. "Tumor location and neurocognitive impairment in adult survivors of pediatric brain tumors: A report from the St. Jude Lifetime Cohort (SJLIFE)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 9531. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.9531.
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9531 Background: Follow-up guidelines identify supratentorial tumor location as a risk factor for poor neurocognitive outcomes during childhood; yet few studies have systematically compared long-term cognitive outcomes between adult survivors of childhood infratentorial and supratentorial brain tumors. Methods: Neurocognitive functions were evaluated in 130 adult survivors of pediatric brain tumors (58 supratentorial and 72 infratentorial, mean [SD] current age = 27.4 years [5.2], age at diagnosis = 8.6 years [4.6], and time since diagnosis = 18.8 years [4.8]) participating in the SJLIFE long-term follow-up protocol. Age-adjusted standard scores for measures of intelligence, attention, memory, processing speed, and executive functioning were calculated, with clinical impairment defined as scores <10th percentile. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models to examine associations between neurocognitive functions and tumor location. Results: As a group, survivors performed below average across multiple neurocognitive domains, including full scale IQ (mean=88.1; SD=18.2), with 34% demonstrating impaired IQ. Survivors of infratentorial tumors were more likely to be impaired on measures of focused attention (OR=2.19, 95% CI=1.03-4.65) and fine motor dexterity (OR=2.62, 95% CI=1.21-5.66) compared to survivors of supratentorial tumors. After adjusting for sex, age at diagnosis, shunt placement and cranial radiation (yes/no), infratentorial tumor location was only associated with reduced performance on a task of visual abstract reasoning (OR=3.76, 95% CI=1.40-10.1). Cranial radiation therapy was independently associated with impaired short-term memory (OR=15.6, 95% CI=1.64-147.8) and processing speed (OR=3.86, 95% CI=1.15-13.0). Conclusions: Tumor location was not associated with neurocognitive impairment after adjusting for treatment exposures. To further delineate potential differences associated with tumor location, future studies will examine factors including radiation dose/volume, extent of surgical resection, and medical complications.
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Yakar, Melek, Durmus Etiz, Muzaffer Metintas, Guntulu Ak, and Ozer Celik. "Prediction of Radiation Pneumonitis With Machine Learning in Stage III Lung Cancer: A Pilot Study." Technology in Cancer Research & Treatment 20 (January 1, 2021): 153303382110163. http://dx.doi.org/10.1177/15330338211016373.
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Background: Radiation pneumonitis (RP) is a dose-limiting toxicity in lung cancer radiotherapy (RT). As risk factors in the development of RP, patient and tumor characteristics, dosimetric parameters, and treatment features are intertwined, and it is not always possible to associate RP with a single parameter. This study aimed to determine the algorithm that most accurately predicted RP development with machine learning. Methods: Of the 197 cases diagnosed with stage III lung cancer and underwent RT and chemotherapy between 2014 and 2020, 193 were evaluated. The CTCAE 5.0 grading system was used for the RP evaluation. Synthetic minority oversampling technique was used to create a balanced data set. Logistic regression, artificial neural networks, eXtreme Gradient Boosting (XGB), Support Vector Machines, Random Forest, Gaussian Naive Bayes and Light Gradient Boosting Machine algorithms were used. After the correlation analysis, a permutation-based method was utilized for as a variable selection. Results: RP was seen in 51 of the 193 cases. Parameters affecting RP were determined as, total(t)V5, ipsilateral lung Dmax, contralateral lung Dmax, total lung Dmax, gross tumor volume, number of chemotherapy cycles before RT, tumor size, lymph node localization and asbestos exposure. LGBM was found to be the algorithm that best predicted RP at 85% accuracy (confidence interval: 0.73-0.96), 97% sensitivity, and 50% specificity. Conclusion: When the clinical and dosimetric parameters were evaluated together, the LGBM algorithm had the highest accuracy in predicting RP. However, in order to use this algorithm in clinical practice, it is necessary to increase data diversity and the number of patients by sharing data between centers.
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Andruska, Neal, Benjamin Walker Fischer-Valuck, Temitope Agabalogun, Ruben Carmona, Randall Brenneman, Hiram Alberto Gay, Jeff M. Michalski, and Brian Christopher Baumann. "Stereotactic body radiation therapy (SBRT) versus conventionally fractionated external beam radiation therapy in unfavorable intermediate-risk prostate cancer: An inverse propensity matched analysis." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e17054-e17054. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e17054.
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e17054 Background: Conventionally fractionated radiotherapy (CFRT) or moderately hypofractionated radiotherapy (MFRT) ± short-course androgen deprivation therapy (ADT) is commonly employed for unfavorable intermediate-risk (UIR) prostate cancer. Stereotactic body radiation therapy (SBRT) has not been widely adopted, but may have radiobiologic advantages over more conventionally fractionated treatments. We hypothesized that radiotherapy dose-escalation with SBRT (35-40Gy in ≤5 fractions) is associated with improved overall survival (OS) relative to biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MFRT (≥60Gy in 2.4-3.2Gy/fraction) ± ADT. Methods: The National Cancer Database (NCDB) was used to identify 28,028 men with UIR prostate cancer who received CFRT with (n = 12,872) or without ADT (n = 12,984), MFRT with (n = 251) or without ADT (n = 281), and SBRT with (n = 212) or without ADT (n = 1,428). SBRT+ADT patients were excluded due to low patient numbers. Inverse probability of treatment weighting was used to balance measured confounders. Unweighted- and weighted- multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios. Results: Relative to CFRT without ADT, CFRT+ADT (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87-0.97], P = .002) and SBRT without ADT (HR: 0.74 [0.61-0.89], P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR: 0.81 [0.67-0.99], P = .04). Weight-adjusted MVA demonstrated that SBRT (HR: 0.80 [0.65-0.98], P = .036) and ADT (HR: 0.91 [0.86-0.97], P = .002) correlated with improved OS. SBRT was not associated with improved OS relative to MFRT. Conclusions: Using inverse propensity treatment weighting, we adjusted for age, comorbidity score, and tumor factors, and observed a significant overall survival benefit in favor of administering dose-escalated SBRT over CFRT+ADT. To our knowledge, this is the first study to show that SBRT is associated with improved OS relative to CFRT for men with UIR prostate cancer. Together, this suggests that SBRT offers a cheaper and shorter course of therapy that mitigates COVID-19 exposure, which also is associated with improved OS relative to CFRT for UIR prostate cancer and may obviate the need for ADT in this population. While we await results from several ongoing clinical trials, we believe this study lends support to the use of SBRT in men with UIR prostate cancer.
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Travis, L. B., J. Weeks, R. E. Curtis, J. T. Chaffey, M. Stovall, P. M. Banks, and J. D. Boice. "Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma." Journal of Clinical Oncology 14, no. 2 (February 1996): 565–71. http://dx.doi.org/10.1200/jco.1996.14.2.565.
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PURPOSE Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. PATIENTS AND METHODS A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. RESULTS Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. CONCLUSIONS Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.
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Kim, Tae Jun, Yeong Chan Lee, Yang Won Min, Hyuk Lee, Byung-Hoon Min, Jun Haeng Lee, Hong-Hee Won, Kyoung Doo Song, Woo Kyoung Jeong, and Jae J. Kim. "Risk of Second Primary Malignancies among Patients with Early Gastric Cancer Exposed to Recurrent Computed Tomography Scans." Cancers 13, no. 5 (March 7, 2021): 1144. http://dx.doi.org/10.3390/cancers13051144.
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Although computed tomography (CT) scans are very useful for identification or surveillance of malignancy, they are also associated with the risk of cancer caused by ionizing radiation. We investigated the risk of second primary malignancies (SPMs) after frequent abdominopelvic CT scans in a cohort of Korean patients with early gastric cancer (EGC). We performed a cohort study of 11,072 patients who underwent resection for EGC at Samsung Medical Center and validated the results using data from 7908 patients in a Korean National Health Insurance Service cohort. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for intra-abdominal SPM. During 43,766.5 person-years of the follow-up at our center, 322 patients developed intra-abdominal SPMs. Patients who underwent receiving >8 abdominopelvic CT scans had a significantly greater risk of developing SPM (HR, 2.73; 95% CI, 1.66–4.50; p < 0.001) than those who had with ≤8 scans. For each additional abdominopelvic CT scan, the adjusted HR for SPM was 1.09 (95% confidence interval (CI), 1.03–1.14). Similar results were observed in the Korean National Health Insurance Service cohort (adjusted HR, 1.14; 95% CI, 1.07–1.22). Significantly elevated risk of SPM was still observed when considering a 2-year latency period (adjusted HR, 2.43; 95% CI, 1.37–4.48) and a 3-year latency period (adjusted HR, 2.17; 95% CI, 1.06–4.47). Frequent abdominopelvic CT scans are associated with an elevated risk of SPMs after the treatment of EGC. Thus, physicians need to weigh carefully the clinical benefits of CT examinations against the potential risks of radiation exposure.