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Articles by M Stovall
Total Records ( 6 ) for M Stovall
  L. R Meacham , C. A Sklar , S Li , Q Liu , N Gimpel , Y Yasui , J. A Whitton , M Stovall , L. L Robison and K. C. Oeffinger
 

Background  Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings.

Methods  Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed between 1970 and 1986 as well as 2936 randomly selected siblings of the survivors. The main outcome was self-reported DM.

Results  The mean ages of the survivors and the siblings were 31.5 years (age range, 17.0-54.1 years) and 33.4 years (age range, 9.6-58.4 years), respectively. Diabetes mellitus was reported in 2.5% of the survivors and 1.7% of the siblings. After adjustment for body mass index, age, sex, race/ethnicity, household income, and insurance, the survivors were 1.8 times more likely than the siblings to report DM (95% confidence interval [CI], 1.3-2.5; P < .001), with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2-25.3; P < .001), abdominal irradiation (OR, 3.4; 95% CI, 2.3-5.0; P < .001), and cranial irradiation (OR, 1.6; 95% CI 1.0-2.3; P = .03) at increased risk. In adjusted models, an increased risk of DM was associated with total body irradiation (OR, 7.2; 95% CI, 3.4-15.0; P < .001), abdominal irradiation (OR, 2.7; 95% CI, 1.9-3.8; P < .001), use of alkylating agents (OR, 1.7; 95% CI, 1.2-2.3; P < .01), and younger age at diagnosis (0-4 years; OR, 2.4; 95% CI, 1.3-4.6; P < .01).

Conclusion  Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to body mass index or physical inactivity.

  G Chodick , R. A Kleinerman , M Stovall , D. H Abramson , J. M Seddon , S. A Smith and M. A. Tucker
 

Objective  To investigate the risk of cataract extraction among adult retinoblastoma survivors.

Design  A retrospective cohort study was performed on retinoblastoma survivors who received the diagnosis from 1914 to 1984 and were interviewed in 2000. Lens doses were estimated from radiotherapy records. The cumulative time interval to cataract extraction between dose groups was compared using the log-rank test and Cox regression.

Results  Seven hundred fifty-three subjects (828 eyes) were available for analysis for an average of 32 years of follow-up. During this period, 51 cataract extractions were reported. One extraction was reported in an eye with no radiotherapy compared with 36 extractions in 306 eyes with 1 course of radiotherapy and 14 among 38 eyes with 2 or 3 treatments. The average time interval to cataract extraction in irradiated eyes was 51 years (95% confidence interval [CI], 48-54) following 1 treatment and 32 years (95% CI, 27-37) after 2 or 3 treatments. Eyes exposed to a therapeutic radiation dose of 5 Gy or more had a 6-fold increased risk (95% CI, 1.3-27.2) of cataract extraction compared with eyes exposed to 2.5 Gy or less.

Conclusions  The results emphasize the importance of ophthalmologic examination of retinoblastoma survivors who have undergone radiotherapy. The risk of cataract extraction in untreated eyes with retinoblastoma is comparable with the risk of the general population.

  C Laverdiere , Q Liu , Y Yasui , P. C Nathan , J. G Gurney , M Stovall , L. R Diller , N. K Cheung , S Wolden , L. L Robison and C. A. Sklar
  Background

The 5-year survival rate for individuals with neuroblastoma is approaching 70%. Few data exist, however, on the long-term outcomes of these patients, who are often treated at a very young age.

Methods

Outcome data were obtained for 954 5-year neuroblastoma survivors who were diagnosed in 1970–1986 and enrolled in the Childhood Cancer Survivor Study (CCSS). Late mortality, second malignant neoplasms, and chronic health conditions were analyzed in relation to treatment factors using Poisson regression models and their modification with generalized estimating equations. Neuroblastoma survivors were compared with a cohort of 3899 siblings of CCSS participants for risk of chronic health conditions and selected sociodemographic outcomes. All statistical tests were two-sided.

Results

Six percent of patients died more than 5 years after their diagnosis (standardized mortality ratio = 5.6; 95% confidence interval [CI] = 4.4 to 6.9). The most common causes of death were disease recurrence (n = 43) and second malignant neoplasms (n = 13). The cumulative incidence of second malignant neoplasms was 3.5% at 25 years and 7.0% at 30 years after diagnosis. Compared with the sibling cohort, survivors had an increased risk of selected chronic health conditions (risk ratio [RR] = 8.3; 95% CI = 7.1 to 9.7) with a 20-year cumulative incidence of 41.1%. The most prevalent outcomes involved the neurological, sensory, endocrine, and musculoskeletal systems, with 20-year cumulative incidences of 29.8%, 8.6%, 8.3%, and 7.8%, respectively. Neuroblastoma survivors who were treated with multimodality therapy were more likely to develop a chronic health condition than survivors treated with surgery alone (RR = 2.2; 95% CI = 1.6 to 3.0). Neuroblastoma survivors were less likely than siblings to have ever been employed (P = .04) or to be married (P < .001) and had a lower personal income (P = .009).

Conclusions

Neuroblastoma survivors have an increased rate of mortality and second malignant neoplasms, relative to the age- and sex-comparable US population, and of chronic health conditions, relative to their siblings, which underscores the need for long-term medical surveillance.

  J. L Bernstein , R. W Haile , M Stovall , J. D Boice , R. E Shore , B Langholz , D. C Thomas , L Bernstein , C. F Lynch , J. H Olsen , K. E Malone , L Mellemkjaer , A. L Borresen Dale , B. S Rosenstein , S. N Teraoka , A. T Diep , S. A Smith , M Capanu , A. S Reiner , X Liang , R. A Gatti , P Concannon and and the WECARE Study Collaborative Group
  Background

Ionizing radiation is a known mutagen and an established breast carcinogen. The ATM gene is a key regulator of cellular responses to the DNA damage induced by ionizing radiation. We investigated whether genetic variants in ATM play a clinically significant role in radiation-induced contralateral breast cancer in women.

Methods

The Women's Environmental, Cancer, and Radiation Epidemiology Study is an international population-based case–control study nested within a cohort of 52 536 survivors of unilateral breast cancer diagnosed between 1985 and 2000. The 708 case subjects were women with contralateral breast cancer, and the 1397 control subjects were women with unilateral breast cancer matched to the case subjects on age, follow-up time, registry reporting region, and race and/or ethnicity. All women were interviewed and underwent full mutation screening of the entire ATM gene. Complete medical treatment history information was collected, and for all women who received radiotherapy, the radiation dose to the contralateral breast was reconstructed using radiotherapy records and radiation measurements. Rate ratios (RRs) and corresponding 95% confidence intervals (CIs) were estimated by using multivariable conditional logistic regression. All P values are two-sided.

Results

Among women who carried a rare ATM missense variant (ie, one carried by <1% of the study participants) that was predicted to be deleterious, those who were exposed to radiation (mean radiation exposure = 1.2 Gy, SD = 0.7) had a statistically significantly higher risk of contralateral breast cancer compared with unexposed women who carried the wild-type genotype (0.01–0.99 Gy: RR = 2.8, 95% CI = 1.2 to 6.5; ≥1.0 Gy: RR = 3.3, 95% CI = 1.4 to 8.0) or compared with unexposed women who carried the same predicted deleterious missense variant (0.01–0.99 Gy: RR = 5.3, 95% CI = 1.6 to 17.3; ≥1.0 Gy: RR = 5.8, 95% CI = 1.8 to 19.0; Ptrend = .044).

Conclusions

Women who carry rare deleterious ATM missense variants and who are treated with radiation may have an elevated risk of developing contralateral breast cancer. However, the rarity of these deleterious missense variants in human populations implies that ATM mutations could account for only a small portion of second primary breast cancers.

  J. P Ginsberg , P Goodman , W Leisenring , K. K Ness , P. A Meyers , S. L Wolden , S. M Smith , M Stovall , S Hammond , L. L Robison and K. C. Oeffinger
  Background

The survival of Ewing sarcoma (ES) patients has improved since the 1970s but is associated with considerable future health risks.

Methods

The study population consisted of long-term (≥5-year) survivors of childhood ES diagnosed before age 21 from 1970 to 1986. Cause-specific mortality was evaluated in eligible survivors (n = 568), and subsequent malignant neoplasms, chronic health conditions, infertility, and health status were evaluated in the subset participating in the Childhood Cancer Survivor Study (n = 403). Outcomes were compared with the US population and sibling control subjects (n = 3899). Logistic, Poisson, or Cox proportional hazards models, with adjustments for sex, age, race/ethnicity, and potential intrafamily correlation, were used. Statistical tests were two-sided.

Results

Cumulative mortality of ES survivors was 25.0% (95% confidence interval [CI] = 21.1 to 28.9) 25 years after diagnosis. The all-cause standardized mortality ratio was 13.3 (95% CI = 11.2 to 15.8) overall, 23.1 (95% CI = 17.6 to 29.7) for women, and 10.0 (95% CI = 7.9 to 12.5) for men. The nonrecurrence-progression non-external cause standardized mortality ratio (subsequent non-ES malignant neoplasms and cardiac and pulmonary causes potentially attributable to ES treatment) was 8.7 (95% CI = 6.2 to 12.0). Twenty-five years after ES diagnosis, cumulative incidence of subsequent malignant neoplasms, excluding nonmelanoma skin cancers, was 9.0% (95% CI = 5.8 to 12.2). Compared with siblings, survivors had an increased risk of severe, life-threatening, or disabling chronic health conditions (relative risk = 6.0, 95% CI = 4.1 to 9.0). Survivors had lower fertility rates (women: P = .005; men: P < .001) and higher rates of moderate to extreme adverse health status (P < .001).

Conclusion

Long-term survivors of childhood ES exhibit excess mortality and morbidity.

 
 
 
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