PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1062641)

Clipboard (0)
None

Related Articles

1.  In Vivo Response to Methotrexate Forecasts Outcome of Acute Lymphoblastic Leukemia and Has a Distinct Gene Expression Profile 
PLoS Medicine  2008;5(4):e83.
Background
Childhood acute lymphoblastic leukemia (ALL) is the most common cancer in children, and can now be cured in approximately 80% of patients. Nevertheless, drug resistance is the major cause of treatment failure in children with ALL. The drug methotrexate (MTX), which is widely used to treat many human cancers, is used in essentially all treatment protocols worldwide for newly diagnosed ALL. Although MTX has been extensively studied for many years, relatively little is known about mechanisms of de novo resistance in primary cancer cells, including leukemia cells. This lack of knowledge is due in part to the fact that existing in vitro methods are not sufficiently reliable to permit assessment of MTX resistance in primary ALL cells. Therefore, we measured the in vivo antileukemic effects of MTX and identified genes whose expression differed significantly in patients with a good versus poor response to MTX.
Methods and Findings
We utilized measures of decreased circulating leukemia cells of 293 newly diagnosed children after initial “up-front” in vivo MTX treatment (1 g/m2) to elucidate interpatient differences in the antileukemic effects of MTX. To identify genomic determinants of these effects, we performed a genome-wide assessment of gene expression in primary ALL cells from 161 of these newly diagnosed children (1–18 y). We identified 48 genes and two cDNA clones whose expression was significantly related to the reduction of circulating leukemia cells after initial in vivo treatment with MTX. This finding was validated in an independent cohort of children with ALL. Furthermore, this measure of initial MTX in vivo response and the associated gene expression pattern were predictive of long-term disease-free survival (p < 0.001, p = 0.02).
Conclusions
Together, these data provide new insights into the genomic basis of MTX resistance and interpatient differences in MTX response, pointing to new strategies to overcome MTX resistance in childhood ALL.
Trial registrations: Total XV, Therapy for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia, http://www.ClinicalTrials.gov (NCT00137111); Total XIIIBH, Phase III Randomized Study of Antimetabolite-Based Induction plus High-Dose MTX Consolidation for Newly Diagnosed Pediatric Acute Lymphocytic Leukemia at Intermediate or High Risk of Treatment Failure (NCI-T93-0101D); Total XIIIBL, Phase III Randomized Study of Antimetabolite-Based Induction plus High-Dose MTX Consolidation for Newly Diagnosed Pediatric Acute Lymphocytic Leukemia at Lower Risk of Treatment Failure (NCI-T93-0103D).
William Evans and colleagues investigate the genomic determinants of methotrexate resistance and interpatient differences in methotrexate response in patients newly diagnosed with childhood acute lymphoblastic leukemia.
Editors' Summary
Background.
Every year about 10,000 children develop cancer in the US. Acute lymphoblastic leukemia (ALL), a rapidly progressing blood cancer, accounts for a quarter of these childhood cancers. Normally, cells in the bone marrow (the spongy material inside bones) develop into lymphocytes (white blood cells that fight infections), red blood cells (which carry oxygen round the body), platelets (which prevent excessive bleeding), and granulocytes (another type of white blood cell). However, in ALL, genetic changes in immature lymphocytes (lymphoblasts) mean that these cells divide uncontrollably and fail to mature. Eventually, the bone marrow fills up with these abnormal cells and can no longer make healthy blood cells. As a result, children with ALL cannot fight infections. They also bruise and bleed easily and, because they do not have enough red blood cells, they often complain of tiredness and weakness. With modern chemotherapy protocols (combinations of drugs that kill the fast-dividing cancer cells but leave the normal, nondividing cells in the body largely unscathed), more than 80% of children with ALL live for at least 5 years.
Why Was This Study Done?
Although this survival rate is good, some patients still die because their cancer cells are resistant to one or more chemotherapy drugs. For some drugs, the genetic characteristics of the ALL cells that make them resistant are known. Unfortunately, little is known about why some ALL cells are resistant to methotrexate, a component of most treatment protocols for newly diagnosed ALL. Methotrexate kills dividing cells by interfering with DNA synthesis and repair. Cancer cells can be resistant to methotrexate for many reasons—they may have acquired genetic changes that stop the drug from entering them, for example. These resistance mechanisms need to be understood better before new strategies can be developed for the treatment of methotrexate-resistant ALL. In this study, the researchers have determined the response of newly diagnosed patients to methotrexate and have investigated the gene expression patterns in ALL cells that correlate with good and bad responses to methotrexate.
What Did the Researchers Do and Find?
The researchers measured the reduction in circulating leukemia cells that followed the first treatment with methotrexate of nearly 300 patients with newly diagnosed ALL. They also used “microarray” analysis to investigate the gene expression patterns in lymphoblast samples taken from the bone marrow of 161 patients before treatment. They found that the expression of 50 genes was significantly related to the reduction in circulating leukemia cells after methotrexate treatment (a result confirmed in an independent group of patients). Of these genes, the expression of 29 was higher in patients who responded poorly to methotrexate than in patients who responded well. A “global analysis test,” which examined the gene expression profile of different cellular pathways in relation to the methotrexate response, found a significant association between the nucleotide biosynthesis pathway (which is needed for DNA synthesis and cellular proliferation) and the methotrexate response. Finally, patients with the best methotrexate response and the 50-gene expression profile indicative of a good response were more likely to be alive after 5 years than patients with the worst methotrexate response and the poor-response gene expression profile.
What Do These Findings Mean?
These findings provide important new insights into the genetic basis of methotrexate resistance in newly diagnosed childhood ALL and begin to explain why some patients fail to respond to this drug. They also show that the reduction in circulating leukemic cells shortly after the first methotrexate dose and a specific gene expression profile both predict the long-term survival of patients. These findings also suggest new ways to modulate sensitivity to methotrexate. Down-regulation of the expression of the genes that are expressed more highly in poor responders than in good responders might improve patient responses to methotrexate. Alternatively, it might be possible to find ways to increase the expression of the genes that are underexpressed in methotrexate poor responders and so improve the outlook for at least some of the children with ALL who fail to respond to current chemotherapy protocols.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050083.
• The US National Cancer Institute provides a fact sheet for patients and caregivers about ALL in children and information about its treatment(in English and Spanish)
• The UK charity Cancerbackup provides information for patients and caregivers on ALL in children and on methotrexate
• The US Leukemia and Lymphoma Society also provides information for patients and caregivers about ALL
• The Children's Cancer and Leukaemia Group (a UK charity) provides information for children with cancer and their families
• MedlinePlus provides additional information about methotrexate (in English and Spanish)
doi:10.1371/journal.pmed.0050083
PMCID: PMC2292747  PMID: 18416598
2.  Adverse Impact of Mood on Flow-Mediated Dilation 
Psychosomatic Medicine  2010;72(2):122-127.
Objective
To examine the impact of mood states on endothelial function, as measured noninvasively by brachial artery flow-mediated dilation (FMD). Substantial literature indicates that negative mood is linked to cardiovascular disease (CVD). However, the mechanisms underlying this relationship are not well defined. CVD is often preceded by dysfunction of the endothelium.
Methods
Healthy adults (n = 70; mean age, 36 years) completed the Profile of Mood States (POMS), which contains six subscales (depression/dejection; tension/anxiety; anger/hostility; confusion/bewilderment; fatigue/inertia; vigor/activity) that are used to compute a total mood disturbance score for overall psychological distress. FMD was calculated (maximum percentage change in brachial artery diameter) from ultrasound assessment of arterial diameter at baseline and for 10 minutes after occlusion.
Results
Regressions showed that increases in POMS total mood disturbance scores were associated with decreases in endothelial function. Mood disturbance explained 10% of the variance in FMD (p < .01), after controlling for age, sex, mean arterial pressure, body mass index, and socially desirable response bias. An exploratory set of separate regressions conducted to decompose the link between FMD and total mood disturbance revealed that the following POMS subscales were inversely correlated with FMD: depression/dejection, tension/anxiety, anger/hostility, fatigue/inertia (p’s < .05), and confusion/bewilderment (p < .01).
Conclusions
Mood disturbance could contribute to CVD via impaired vasodilation. These preliminary results show that even mild levels of adverse psychological states, particularly depressed, anxious, angry, confused, and fatigued states, might be linked to increased cardiovascular risk.
doi:10.1097/PSY.0b013e3181cdbfc0
PMCID: PMC3163844  PMID: 20100885
endothelial function; vasodilation; mood; depression; anxiety; fatigue
3.  Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study 
Journal of Clinical Oncology  2013;31(35):4407-4415.
Purpose
To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).
Patients and Methods
Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.
Results
Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.
Conclusion
This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.
doi:10.1200/JCO.2012.48.2315
PMCID: PMC3842908  PMID: 24190124
4.  Comparison of intelligence quotient in children surviving leukemia who received different prophylactic central nervous system treatments 
Background:
Neurocognitive deficits and decrease in intelligence quotient (IQ) is one of the complication of prophylactic central nervous system (CNS) treatment in acute lymphoblastic leukemia (ALL) patients. In this study, we compare the IQ in survivors of ALL that were treated with different prophylactic CNS treatments.
Materials and Methods:
We compared 43 long-term survivors of ALL: 21 survivors with intrathecal methotrexate (IT MTX) as CNS prophylaxis, 22 with IT MTX+1800-2400 rads cranial irradiation and 20 healthy controls. The IQ was measured using the Raven's test in these patients.
Results:
Raven's test revealed significant differences in IQ between the survivors of ALL that were treated with IT MTX, IT MTX plus cranial irradiation and control group. There was no significant difference in the IQ with respect to sex, age and irradiation dose.
Conclusion:
We can that reveal that CNS prophylaxis treatment, especially the combined treatment, is associated with IQ score decline in ALL survivors. Therefore,a baseline and an annual assessment of their educational progress are suggested.
doi:10.4103/2277-9175.103005
PMCID: PMC3544107  PMID: 23326813
Acute lymphoblastic leukemia; chemotherapy; intelligence quotient; radiotherapy
5.  Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia. 
British Journal of Cancer  1996;73(6):825-830.
Long-term cognitive and educational sequelae have been inconsistently reported in children who received cranial irradiation (CRT) to prevent central nervous system (CNS) disease in acute lymphoblastic leukaemia (ALL). This study investigates a large and representative sample of survivors of ALL and compares them with non-irradiated survivors of cancer and healthy control children to determine the effect of CRT on cognitive and educational ability. Three groups of children were studied: Group 1 (n=100) survivors of ALL treated with chemotherapy and CRT, group 2 (n=50) children with a variety of malignancies treated with chemotherapy alone, group 3(n=100) healthy children. Cognitive and educational abilities of these groups were evaluated using standardised psychometric techniques. Significant differences in cognitive and educational abilities were found between the children in group 1 (chemotherapy + CRT) and the two control groups, with the children receiving CRT performing less well in a range of tests. Greatest differences were detected for tasks dependent on language function including verbal IQ, reading and spelling. Within group 1 a younger age at treatment (less than 5 years) and a higher dose of CRT (24 Gy vs 18 Gy) were predictive of poor long-term outcome for cognitive and education ability. In contrast, children who received chemotherapy alone, with or without intrathecal methotrexate, performed similarly to healthy controls. No gender differences were detected for these measures.
PMCID: PMC2074370  PMID: 8611389
6.  Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia: associations with physical performance and chemotherapy doses 
Cancer  2011;118(3):828-838.
Introduction
Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. This study examined associations between neuromuscular impairments and physical function, and between neuromuscular impairments, and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL.
Methods
ALL survivors 10+ years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments and physical performance.
Results
Among 415 survivors (median age 35 years; range 21–52), balance, mobility and six-minute walk (6MW) distances were 1.3 standard deviations below age- and sex-specific values in 15.4%, 3.6% and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) < 5 degrees (33.5%) and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors treated with intrathecal methotrexate cumulative doses 215+ mg/m2 were 3.4 (95% CI 1.2–9.8) times more likely than survivors who received no intrathecal methotrexate, and those who received vincristine cumulative doses 39+ mg/m2 1.5 (95% CI 1.0–2.5) times more likely than those who received lower doses to have impaired ROM. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances.
Conclusion
Neuromuscular impairments are prevalent in childhood ALL survivors and interfere with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate are associated with long-term neuromuscular impairments, which have implications on future function as these survivors age.
doi:10.1002/cncr.26337
PMCID: PMC3197897  PMID: 21766297
Acute Lymphoblastic Leukemia; Survivor; Neuromuscular impairment; Function; Physical performance; Intrathecal methotrexate; Vincristine; Late effect
7.  Reduced Cardiorespiratory Fitness in Adult Survivors of Childhood Acute Lymphoblastic Leukemia 
Pediatric blood & cancer  2013;60(8):10.1002/pbc.24492.
Background
Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited.
Procedure
To assess cardiorespiratory fitness, maximal oxygen uptake (VO2max) was measured in 115 ALL survivors (median age, 23.5 years; range 18–37). We compared VO2max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003–2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest.
Results
Compared to NHANES participants, ALL survivors had a substantially lower VO2max (mean 30.7 vs 39.9 ml/kg/min; adjusted P<0.0001). For any given percent total body fat, ALL survivors had an 8.9 ml/kg/min lower VO2max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2max compared with NHANES participants (all comparisons, P<0.001). Almost two-thirds (66.7%) of ALL survivors were classified as low cardiorespiratory fitness compared with 26.3% of NHANES participants (adjusted P<0.0001). In multivariable models including only ALL survivors, treatment exposures were modestly associated with VO2max. Among females, CRT was associated with low VO2max (P=0.02), but anthracycline exposure was not (P=0.58). In contrast, among males, anthracycline exposure ≥100 mg/m2 was associated with low VO2max (P=0.03), but CRT was not (P=0.54).
Conclusion
Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population.
doi:10.1002/pbc.24492
PMCID: PMC3725590  PMID: 23418044
childhood cancer; acute lymphoblastic leukemia; survivor; cardiorespiratory fitness
8.  Psychological Status in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;27(14):2396-2404.
Psychological quality of life (QOL), health-related QOL (HRQOL), and life satisfaction outcomes and their associated risk factors are reviewed for the large cohort of survivors and siblings in the Childhood Cancer Survivor Study (CCSS). This review includes previously published manuscripts that used CCSS data focused on psychological outcome measures, including the Brief Symptom Inventory (BSI-18), the Medical Outcomes Survey Short Form-36 (SF-36), the Cantril Ladder of Life, and other self-report questionnaires. Comparisons and contrasts are made between siblings and survivors, and to normative data when available, in light of demographic/health information and abstracted data from the medical record. These studies demonstrate that a significant proportion of survivors report more symptoms of global distress and poorer physical, but not emotional, domains of HRQOL. Other than brain tumor survivors, most survivors report both good present and expected future life satisfaction. Risk factors for psychological distress and poor HRQOL are female sex, lower educational attainment, unmarried status, annual household income less than $20,000, unemployment, lack of health insurance, presence of a major medical condition, and treatment with cranial radiation and/or surgery. Cranial irradiation impacted neurocognitive outcomes, especially in brain tumor survivors. Psychological distress also predicted poor health behaviors, including smoking, alcohol use, fatigue, and altered sleep. Psychological distress and pain predicted use of complementary and alternative medicine. Overall, most survivors are psychologically healthy and report satisfaction with their lives. However, certain groups of childhood cancer survivors are at high risk for psychological distress, neurocognitive dysfunction, and poor HRQOL, especially in physical domains. These findings suggest targeting interventions for groups at highest risk for adverse outcomes and examining the positive growth that remains despite the trauma of childhood cancer.
doi:10.1200/JCO.2008.21.1433
PMCID: PMC2677925  PMID: 19255309
9.  Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report from the Childhood Cancer Survivor Study 
Neuropsychology  2009;23(6):705-717.
Background
Among survivors of childhood cancer, those with Central Nervous System (CNS) malignancies have been found to be at greatest risk for neuropsychological dysfunction in the first few years following diagnosis and treatment. This study follows survivors to adulthood to assess the long term impact of childhood CNS malignancy and its treatment on neurocognitive functioning.
Participants & Methods
As part of the Childhood Cancer Survivor Study (CCSS), 802 survivors of childhood CNS malignancy, 5937 survivors of non-CNS malignancy and 382 siblings without cancer completed a 25 item Neurocognitive Questionnaire (CCSS-NCQ) at least 16 years post cancer diagnosis assessing task efficiency, emotional regulation, organizational skills and memory. Neurocognitive functioning in survivors of CNS malignancy was compared to that of non-CNS malignancy survivors and a sibling cohort. Within the group of CNS malignancy survivors, multiple linear regression was used to assess the contribution of demographic, illness and treatment variables to reported neurocognitive functioning and the relationship of reported neurocognitive functioning to educational, employment and income status.
Results
Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all factors assessed by the CCSS-NCQ than non-CNS cancer survivors or siblings (p<.01), with mean T scores of CNS malignancy survivors substantially more impaired that those of the sibling cohort (p<.001), with a large effect size for Task Efficiency (1.16) and a medium effect size for Memory (.68). Within the CNS malignancy group, medical complications, including hearing deficits, paralysis and cerebrovascular incidents resulted in a greater likelihood of reported deficits on all of the CCSS-NCQ factors, with generally small effect sizes (.22-.50). Total brain irradiation predicted greater impairment on Task Efficiency and Memory (Effect sizes: .65 and .63, respectively), as did partial brain irradiation, with smaller effect sizes (.49 and .43, respectively). Ventriculoperitoneal (VP) shunt placement was associated with small deficits on the same scales (Effect sizes: Task Efficiency .26, Memory .32). Female gender predicted a greater likelihood of impaired scores on 2 scales, with small effect sizes (Task Efficiency .38, Emotional Regulation .45), while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor with a moderate effect size (.64). CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p<.01), less household income (p<.001) and less full time employment (p<.001).
Conclusions
Survivors of childhood CNS malignancy are at significant risk for impairment in neurocognitive functioning in adulthood, particularly if they have received cranial radiation, had a VP shunt placed, suffered a cerebrovascular incident or are left with hearing or motor impairments. Reported neurocognitive impairment adversely affected important adult outcomes, including education, employment, income and marital status.
doi:10.1037/a0016674
PMCID: PMC2796110  PMID: 19899829
Neurocognitive functioning; brain tumors; CNS malignancies; Childhood Cancer Survivor Study
10.  Fractures among long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study 
Cancer  2012;118(23):5920-5928.
Background
Although reductions in bone mineral density are well-documented among children during treatment for cancer and among childhood cancer survivors, little is known about the long-term risk of fracture. The aim of this study was to ascertain the prevalence of and risk factors for fractures among individuals participating in the Childhood Cancer Survivor Study (CCSS).
Methods
Analyses included 7414 5+ year survivors of childhood cancer diagnosed between 1970-86 who completed the 2007 CCSS follow-up questionnaire and a comparison group of 2374 siblings. Generalized linear models stratified by sex were used to compare the prevalence of reported fractures between survivors and siblings.
Results
The median ages at follow-up among survivors and siblings were 36.2, (range: 21.2-58.8) and 38.1 years (range: 18.4-62.6), respectively with a median 22.7 years of follow-up after cancer diagnosis for survivors. Approximately 35% of survivors and 39% of siblings reported ≥1 fractures during their lifetime. The prevalence of fractures was lower among survivors than siblings, both in males (prevalence ratio=0.87, 95%CI=0.81-0.94, p<0.001) and females (prevalence ratio=0.94, 95%CI=0.86-1.04, p=0.22). In multivariable analyses, increasing age at follow-up, white race, methotrexate treatment and balance difficulties were associated with increased prevalence of fractures among female survivors (p=0.05). Among males, only smoking history and white race were associated with an increased prevalence of fracture (p<0.001).
Conclusions
Findings from this study indicate that the prevalence of fractures among adult survivors is not increased compared to that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted.
doi:10.1002/cncr.27626
PMCID: PMC3439597  PMID: 22605509
11.  Radiation, Atherosclerotic Risk Factors and Stroke Risk in Survivors of Pediatric Cancer: a Report from the Childhood Cancer Survivor Study 
Background
The impact of childhood cranial radiation therapy (CRT) on stroke risk in adulthood, and the role of modifiable atherosclerotic risk factors, remains poorly defined. We assessed long-term incidence rates and stroke risk factors in survivors of childhood cancer followed by the Childhood Cancer Survivor Study (CCSS).
Patients and Methods
CCSS is a multi-institutional retrospective cohort study of 14,358 five-year survivors of childhood cancer and 4,023 randomly selected sibling controls with longitudinal follow up. Age-adjusted incidence rates of self-reported late-occurring (≥ 5 years after diagnosis) first-stroke were calculated. Multivariable Cox Proportional Hazards models were used to identify independent stroke predictors.
Results
During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% Confidence Interval [CI] 62–96) compared to 9.3 (95% CI 4–23) for siblings. Treatment with CRT increased stroke risk in a dose dependent manner: hazard ratio (HR) 5.9 (95% CI 3.5–9.9) for 30–49 Gy CRT, and 11.0 (7.4–17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4–1.8) at 10 years post-diagnosis and 12% (95% CI 8.9–15.0) at 30 years. Hypertension (HTN) increased stroke hazard by 4-fold (95% CI 2.8–5.5) and in black survivors by 16-fold (95% CI 6.9–36.6).
Conclusion
Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.
doi:10.1016/j.ijrobp.2013.03.034
PMCID: PMC3696633  PMID: 23680033
12.  Psychosocial Adjustment Among Cancer Survivors: Findings From a National Survey of Health and Well-Being 
Objective
The current study examined whether cancer survivors showed impairment, resilience, or growth responses relative to a sociodemographically matched sample in four domains: mental health and mood, psychological well-being, social well-being, and spirituality. The impact of aging on psychosocial adjustment was also investigated.
Design
Participants were 398 cancer survivors who were participants in the MIDUS survey (Midlife in the United States) and 796 matched respondents with no cancer history. Psychosocial assessments were completed in 1995-96 and 2004-06.
Results
Findings indicated that cancer survivors demonstrated impairment relative to the comparison group in mental health, mood, and some aspects of psychological well-being. Longitudinal analyses spanning pre- and post-diagnosis clarified that while mental health declined after a cancer diagnosis, poorer functioning in other domains existed prior to diagnosis. However, survivors exhibited resilient social well-being, spirituality, and personal growth. Moreover, age appeared to confer resiliency; older survivors were more likely than younger adults to show psychosocial functioning equivalent to their peers.
Conclusion
While younger survivors may be at risk for disturbances in mental health and mood, cancer survivors show resilience in other important domains of psychosocial adjustment.
doi:10.1037/a0013221
PMCID: PMC2668871  PMID: 19290706
cancer; mental health; mood; resilience; aging
13.  Unemployment among Adult Survivors of Childhood Cancer: A report from the Childhood Cancer Survivors Study 
Medical care  2010;48(11):1015-1025.
Background
Adult childhood cancer survivors report high levels of unemployment although it is unknown whether this is due to health or employability limitations.
Objectives
We examined two employment outcomes from 2002–2005 in the Childhood Cancer Survivor Study (CCSS): 1. health-related unemployment and 2. unemployed but seeking work. We compared survivors to a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome.
Methods
We studied 6339 survivors and 2280 siblings aged ≥25 years excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment.
Results
Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR] 6.07, 95% Confidence Interval [CI] 4.32–8.53). Survivors (5.0%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR 1.90, 95% CI 1.43–2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR] 1.73, 95% CI 1.43–2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR 3.47, 95% CI 2.54–4.74; seeking work: OR 1.77, 95% CI 1.15–2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings.
Conclusions
Childhood cancer survivors have higher levels of unemployment due to health or being between jobs. High-risk survivors may need vocational assistance.
doi:10.1097/MLR.0b013e3181eaf880
PMCID: PMC3428202  PMID: 20940653
14.  Negative moods correlate with craving in female methamphetamine users enrolled in compulsory detoxification 
Background
Methamphetamine (METH) use, especially in females, has become a growing public health concern in China. In this study, we aimed to characterize the factors that contributed to drug craving in female METH users under isolated compulsory detoxification. We characterized factors contributing to craving such as duration of detoxification, history of drug use and self-reported mood state.
Methods
Subjects (N=113) undergoing a 1- to 3-year METH detoxification program were recruited from the Zhejiang Compulsory Detoxification Center for Women. The Questionnaire of METH-use Urge (QMU) was used to evaluate the level of craving for METH. The Abbreviate Profile of Mood States (A-POMS) was applied as an assessment for the negative mood disturbances.
Results
The participants were at a mean age of 25.2, primarily lowly educated and unemployed, and single. Smoking was the only route of METH administration at an average dose of 0.5 g/day, and 4 times/week. The reported craving level was positively correlated with the negative mood disturbances and the weekly dose of METH, but independent of the duration of detoxification. Furthermore, all five aspects of negative mood disturbances, including fatigue, bewilderment, anxiety, depression and hostility, were shown to positively correlate to the self-reported craving level after controlling for weekly dose of METH.
Conclusions
The data demonstrate a robust correlation between mood distress and craving for METH. Our results call for close evaluation of mood distress in treatment of METH users in China.
doi:10.1186/1747-597X-7-44
PMCID: PMC3551715  PMID: 23110820
Methamphetamine; Addiction; Craving; Mood distress; Detoxification
15.  Late-Occurring Neurologic Sequelae in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;28(2):324-331.
Purpose
Children with acute lymphoblastic leukemia (ALL) are often cured, but the therapies they receive may be neurotoxic. Little is known about the incidence and severity of late-occurring neurologic sequelae in ALL survivors. Data were analyzed to determine the incidence of adverse long-term neurologic outcomes and treatment-related risk factors.
Patients and Methods
We analyzed adverse neurologic outcomes that occurred after diagnosis in 4,151 adult survivors of childhood ALL who participated in the Childhood Cancer Survivor Study (CCSS), a retrospective cohort of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings served as a comparison group. Self-reported auditory-vestibular-visual sensory deficits, focal neurologic dysfunction, seizures, and serious headaches were assessed.
Results
The median age at outcome assessment was 20.2 years for survivors. The median follow-up time to death or last survey since ALL diagnosis was 14.1 years. Of the survivors, 64.5% received cranial radiation and 94% received intrathecal chemotherapy. Compared with the sibling cohort, survivors were at elevated risk for late-onset auditory-vestibular-visual sensory deficits (rate ratio [RR], 1.8; 95% CI, 1.5 to 2.2), coordination problems (RR, 4.1; 95% CI, 3.1 to 5.3), motor problems (RR, 5.0; 95% CI, 3.8 to 6.7), seizures (RR, 4.6; 95% CI, 3.4 to 6.2), and headaches (RR, 1.6; 95% CI, 1.4 to 1.7). In multivariable analysis, relapse was the most influential factor that increased risk of late neurologic complications.
Conclusion
Children treated with regimens that include cranial radiation for ALL and those who suffer a relapse are at increased risk for late-onset neurologic sequelae.
doi:10.1200/JCO.2009.22.5060
PMCID: PMC2815720  PMID: 19917844
16.  Symptom Burden in Cancer Survivors One Year after Diagnosis: A Report from the American Cancer Society’s Studies of Cancer Survivors 
Cancer  2011;117(12):2779-2790.
Background
Few studies have examined risk for severe symptoms during early cancer survivorship. Using baseline data from the American Cancer Society’s Study of Cancer Survivors-I, we examined cancer survivors with high symptom burden, identified risk factors associated with high symptom burden, and evaluated the impact of high symptom burden on health-related quality of life (HRQoL) 1 year post-diagnosis.
Methods
Participants were enrolled from 11 state cancer registries approximately 1 year after diagnosis and surveyed by telephone or mail. Outcomes measures were the Modified Rotterdam Symptom Checklist and Profile of Mood States-37 (to assess symptom burden) and the Satisfaction with Life Domains Scale-Cancer (to assess HRQoL).
Results
Of 4903 survivors, 4512 (92%) reported symptoms related to their cancer and/or its treatment. Two-step clustering yielded 2 sub-groups, one with low symptom burden (n=3113) and one with high symptom burden (n=1399). Variables associated with high symptom burden included metastatic cancer (odds ratio [OR], 2.05), number of comorbid conditions (OR, 1.76), remaining on active chemotherapy (OR, 1.93), younger age (OR, 2.31), lacking insurance/being underinsured (OR, 1.57), having lower income (OR, 1.61), being unemployed (OR, 1.27), or being less educated (OR, 1.29). Depression, fatigue, and pain had the greatest impact on HRQoL in survivors with high symptom burden, who also had lower HRQoL (P < .0001).
Conclusions
More than 1 in 4 cancer survivors had high symptom burden 1 year post-diagnosis, even after treatment termination. These results indicate a need for continued symptom monitoring and management in early posttreatment survivorship, especially for the underserved.
doi:10.1002/cncr.26146
PMCID: PMC3143572  PMID: 21495026
cancer survivorship; symptom burden; late effects; risk factors; quality of life; cluster analysis
17.  Longitudinal Changes in Obesity and Body Mass Index Among Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2008;26(28):4639-4645.
Purpose
We examined the rate of increase in the body mass index (BMI; kg/m2) after final height attainment in survivors of acute lymphoblastic leukemia (ALL) and a noncancer comparison group.
Methods
Childhood Cancer Survivor Study (CCSS) is a retrospectively ascertained cohort study that prospectively tracks the health status of adults who were diagnosed with childhood cancer between 1970 and 1986 and a comparison group of siblings. Changes in BMI from baseline enrollment to time of completion of follow-up (mean interval, 7.8 years) were calculated for 1,451 ALL survivors (mean age, 32.3 years at follow-up) and 2,167 siblings of childhood cancer survivors (mean age, 35.9 years).
Results
The mean BMI of the CCSS sibling comparison group increased with age (women, 0.25 units/yr, 95% CI, 0.22 to 0.28 units; men, 0.23 units/yr, 95% CI, 0.20 to 0.25 units). Compared with CCSS siblings, ALL survivors who were treated with cranial radiation therapy (CRT) had a significantly greater increase in BMI (women, 0.41 units/yr, 95% CI, 0.37 to 0.45 units; men, 0.29 units/yr; 95% CI, 0.26 to 0.32 units). The rate of BMI increase was not significantly increased for ALL survivors who were treated with chemotherapy alone. Younger age at CRT exposure significantly modified risk.
Conclusion
CRT used in the treatment of childhood ALL is associated with a greater rate of increasing BMI, particularly among women treated with CRT during the first decade of life. Health care professionals should be aware of this risk and interventions to reduce or manage weight gain are essential in this high-risk population.
doi:10.1200/JCO.2008.16.3527
PMCID: PMC2653124  PMID: 18824710
18.  Incidental Detection of Late Subsequent Intracranial Neoplasms with Magnetic Resonance Imaging Among Adult Survivors of Childhood Cancer 
Purpose
Survivors of childhood cancer are at increased risk of developing subsequent neoplasms. In long term survivors of childhood malignancies treated with and without cranial radiation therapy (CRT), undergoing unenhanced magnetic resonance imaging (MRI) of the brain, we estimated detection of intracranial neoplasms.
Methods
To investigate neurocognitive outcomes, 219 survivors of childhood cancer underwent unenhanced screening MRI of the brain. 164 of the survivors had been treated for acute lymphoblastic leukemia (ALL) (125 received CRT), and 55 for Hodgkin lymphoma (HL) (none received CRT). MRI examinations were reviewed and systematically coded by a single neuroradiologist. Demographic and treatment characteristics were compared for survivors with and without subsequent neoplasms.
Results
Nineteen of the 219 survivors (8.7%) had a total of 31 subsequent intracranial neoplasms identified by neuroimaging at a median time of 25 years (range 12-46 years) from diagnosis. All neoplasms occurred after CRT, except for a single vestibular schwannoma within the cervical radiation field in a HL survivor. The prevalence of subsequent neoplasms after CRT exposure was 14.4% (18 of 125). By noncontrast MRI, intracranial neoplasms were most suggestive of meningiomas. Most patients presented with no specific, localizing neurological complaints. In addition to the schwannoma, six tumors were resected based on results of MRI screening, all of which were meningiomas on histologic review.
Conclusion
Unenhanced brain MRI of long-term survivors of childhood cancer detected a substantial number of intracranial neoplasms. Screening for early detection of intracranial neoplasms among aging survivors of childhood cancer who received CRT should be evaluated.
Implications for Cancer Survivors
The high prevalence of incidentally detected subsequent intracranial neoplasms after CRT in long-term survivors of childhood cancer and the minimal symptoms reported by those with intracranial tumors in our study indicate that brain MRI screening of long-term survivors who received CRT may be warranted. Prospective studies of such screening are needed.
doi:10.1007/s11764-014-0344-8
PMCID: PMC4119575  PMID: 24488818
Survivors of Childhood Cancer; Cranial Radiation Therapy; Subsequent Intracranial Neoplasms; Meningiomas
19.  Investigating efficacy of two brief mind–body intervention programs for managing sleep disturbance in cancer survivors: a pilot randomized controlled trial 
Journal of Cancer Survivorship  2013;7(2):165-182.
Purpose
After completing treatment, cancer survivors may suffer from a multitude of physical and mental health impairments, resulting in compromised quality of life. This exploratory study investigated whether two mind–body interventions, i.e., Mind–Body Bridging (MBB) and Mindfulness Meditation (MM), could improve posttreatment cancer survivors’ self-reported sleep disturbance and comorbid symptoms, as compared to sleep hygiene education (SHE) as an active control.
Methods
This randomized controlled trial examined 57 cancer survivors with clinically significant self-reported sleep disturbance, randomly assigned to receive MBB, MM, or SHE. All interventions were conducted in three sessions, once per week. Patient-reported outcomes were assessed via the Medical Outcomes Study Sleep Scale and other indicators of psychosocial functioning relevant to quality of life, stress, depression, mindfulness, self-compassion, and well-being.
Results
Mixed effects model analysis revealed that mean sleep disturbance symptoms in the MBB (p = .0029) and MM (p = .0499) groups were lower than in the SHE group, indicating that both mind–body interventions improved sleep. In addition, compared with the SHE group, the MBB group showed reductions in self-reported depression symptoms (p = .040) and improvements in overall levels of mindfulness (p = .018), self-compassion (p = .028), and well-being (p = .019) at postintervention.
Conclusions
This study provides preliminary evidence that brief sleep-focused MBB and MM are promising interventions for sleep disturbance in cancer survivors. Integrating MBB or MM into posttreatment supportive plans should enhance care of cancer survivors with sleep disturbance. Because MBB produced additional secondary benefits, MBB may serve as a promising multipurpose intervention for posttreatment cancer survivors suffering from sleep disturbance and other comorbid symptoms.
Implications for Cancer Survivors
Two brief sleep-focused mind–body interventions investigated in the study were effective in reducing sleep disturbance and one of them further improved other psychosocial aspects of the cancer survivors’ life. Management of sleep problems in survivors is a high priority issue that demands more attention in cancer survivorship.
doi:10.1007/s11764-012-0252-8
PMCID: PMC3622018  PMID: 23338490
Mind–body bridging; Mindfulness meditation; Cancer survivors; Sleep disturbance; Depression; Quality of life
20.  Distress among young adult cancer survivors: a cohort study 
Purpose
Being diagnosed with cancer as a young adult can lead to significant psychological distress and impaired quality of life. Compared to children and older adults diagnosed with cancer, fewer studies have addressed psychological distress among young adult cancer survivors. This study sought to identify the prevalence of, and factors associated with, distress among young adult cancer survivors (ages 18–39).
Methods
Young adult cancer survivors (N=335, mean age= 31.8, women=68.4 %) were recruited from an online research panel and stratified by cohort (time postactive treatment: 0–12, 13–24, and 25–60 months). Participants completed measures assessing demographic and clinical characteristics, global impact of cancer, cancer-related education and work interruption, and cancer-specific distress using the impact of event scale (IES).
Results
The mean score on the IES (M=31.0, range=0–75) was above the cut point of 20, suggesting clinically elevated distress. Analysis of covariance revealed significant main effects for cohort, global impact and cancer-related education/work interruption, and an interaction between cohort and cancer-related education/work interruption on distress. Although there was no significant effect of education/work interruption on distress for those in the 0–12 month cohort (p=.88), survivors in the 13–24 and 25–60 month cohorts reporting education/work interruption were significantly more distressed than those not reporting education/work interruption in the respective cohorts (p<.05).
Conclusions
Young adult cancer survivors face unique challenges. These data underscore the importance of attending to cancer-related distress beyond the completion of treatment and may help inform targeted interventions to prevent or reduce significant distress and related sequelae in this population.
doi:10.1007/s00520-013-1793-8
PMCID: PMC3835730  PMID: 23568764
Young adults; Survivorship; Cancer; Distress; Psychosocial
21.  Relationship of serum methotrexate concentration in high-dose methotrexate chemotherapy to prognosis and tolerability: A prospective cohort study in chinese adults with osteosarcoma 
Background: Cancer that originates in the bone, termed primary bone cancer, is rare. Osteosarcoma (OS) occurs primarily in growing bone tissue and is more prevalent in children and adolescents. OS in adults is rare, with 3 to 5 cases per million population per year worldwide. There are limited data on treatment-related prognosis and adverse reactions in adults reported in the literature.
Objectives: The aims of this study were to investigate factors that influence serum methotrexate (MTX) concentrations used in chemotherapy in Chinese adult patients with OS, and to determine the correlations (based on age, sex, and dosage), if any, between MTX and prognosis, in terms of disease-free survival (DFS) and overall survival (OAS), and tolerability.
Methods: Adult patients aged ≥30 years with OS received ≥3 courses (2 courses before surgery and 3–4 courses postsurgery) of high-dose MTX (6 or 8 g/m2) combined chemotherapy. The regimen consisted of day 1: MTX + folinic acid (herein referred to as citrovorum factor rescue); day 8: cisplatin; days 21 to 25: ifosfamide + mesna; and day 21: doxorubicin. Serum MTX concentrations were assessed immediately after the end of infusion (baseline) and at 24 and 48 hours using high-performance liquid chromatography. Changes in serum MTX concentrations, factors that influence serum MTX concentrations, and the relationship between serum MTX concentrations and prognosis and tolerability (determined by adverse reactions) were analyzed. Patients received a second course of treatment after a 3-week period.
Results: Ninety patients (58 men, 32 women; age range, 30–67 years) with OS were included in the study. A total of 532 courses of combined chemotherapy were administered. The serum MTX concentrations ranged widely at baseline (244.31–929.68 mol/L, Cmin and Cmax, respectively) and at 24 hours (0.73–28.24 mol/L, respectively), suggesting that the serum MTX concentrations varied significantly between different individuals and within the same individual at different time points. The serum MTX concentrations in ~23% of cases (122/532) determined at 24 and/or 48 hours were numerically higher than the safety values (according to Nirenberg's reference: irreversible damage if MTX concentration was >10 umol/L and > 1 umol/L at 24 and 48 hours, respectively). No correlation was found between high serum MTX concentration at baseline and high serum MTX concentration at 24 hours (r = 0.401). The prevalences of the 3 most common adverse reactions in these patients were depressed white blood cell count (44.03%), dental ulcer (23.0%), and rash (18.0%). However, in the remaining 410 courses in which serum MTX concentrations were lower than the safety values, these prevalences were 14.6%, 3–9%, and 2.4%, respectively. Neither age nor sex was significantly associated with MTX Cmax, but dosage was (P < 0.05). Patients with a serum MTX Cmax concentration >500 μmol/L at baseline had a significantly longer DFS rate than those with ≤500 umol/L (P = 0.040). There were no significant between-group differences in the OAS rates.
conclusions: In these Chinese patients with OS, serum MTX concentrations measured at different time points were varied. The findings suggest that adverse reactions occurred in patients whose serum MTX concentrations at 24 and/or 48 hours were higher than the safety values. The dosage appeared to have influenced MTX Cmax, while sex and age did not, and the Cmax was significantly related to DFS but not OAS.
doi:10.1016/j.curtheres.2009.04.005
PMCID: PMC3967322  PMID: 24683226
osteosarcoma; MTX; serum concentration; prognosis; side effect
22.  Psychological Outcomes of Siblings of Cancer Survivors: A Report from the Childhood Cancer Survivor Study 
Psycho-oncology  2010;20(12):1259-1268.
Objective
To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer.
Methods
Cross-sectional, self-report data from 3,083 adult siblings (mean age 29 years, range 18-56 years) of 5+ year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression.
Results
Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98).
Conclusions
These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.
doi:10.1002/pon.1848
PMCID: PMC3223600  PMID: 22114043
23.  HEALTH-RELATED QUALITY OF LIFE AMONG EARLY-STAGE, NON-SMALL CELL, LUNG CANCER SURVIVORS 
Background
Limited data are available about the physical and mental functioning of individuals diagnosed and treated for early stage lung cancer. To develop post-treatment guidelines and targeted resources for the growing number of lung cancer survivors, clinically relevant information about longer-term health-related quality of life (HQOL) is needed. The current study examines lung cancer survivors' HQOL and identifies associations between HQOL and demographic, disease and psychosocial risk factors.
Methods
A total of 359 individuals diagnosed and surgically treated for Stage IA or IB non-small cell lung cancer completed a post-treatment survey via mail or telephone that included the SF-36v2 as well as demographic, medical, psychological and physical symptom indices. To better understand the impact of lung cancer treatment, we examined age- and gender-adjusted differences in HQOL as compared to a demographically matched sample of older adults, most with a significant smoking history, who participated in a lung cancer screening trial. Risk factors for impairments in HQOL were also identified.
Results
Compared to the screening sample, lung cancer survivors reported lower physical health scores, but did not differ in terms of mental health status. Dyspnea and distressed mood were most associated with HQOL impairments.
Conclusions
Early stage lung cancer survivors are likely to experience mild impairment in physical functioning. They may benefit from management of distressed mood and referral to physical activity and pulmonary rehabilitation programs to promote HQOL outcomes.
doi:10.1016/j.lungcan.2010.04.011
PMCID: PMC3470856  PMID: 20462654
quality of life; lung cancer; survivorship
24.  Prevalence and Predictors of Posttraumatic Stress Disorder in Adult Survivors of Childhood Cancer: a report from the Childhood Cancer Survivor Study 
Pediatrics  2010;125(5):e1124-e1134.
Objective
Recent studies have found that a subset of young adult survivors of childhood cancer report posttraumatic stress symptoms in response to their diagnosis and treatment. However, it is unclear if these symptoms are associated with impairment in daily functions and/or significant distress, thereby resulting in a clinical disorder. Furthermore, it is unknown whether this disorder continues into very long-term survivorship, including the 3rd and 4th decades of life. This study hypothesized that very long-term survivors of childhood cancer would be more likely to report symptoms of posttraumatic stress disorder, with functional impairment and/or clinical distress, compared to a group of healthy siblings.
Patients and Methods
6,542 childhood cancer survivors over the age of 18 who were diagnosed between 1970 and 1986 and 368 siblings of cancer survivors completed a comprehensive demographic and health survey.
Results
589 survivors (9%) and 8 siblings (2%) reported functional impairment and/or clinical distress in addition to the set of symptoms consistent with a full diagnosis of Posttraumatic Stress Disorder (PTSD). Survivors had more than a four-fold risk of PTSD compared to siblings (OR=4.14, 95%CI: 2.08-8.25). Controlling for demographic and treatment variables, increased risk of PTSD was associated with educational level of high school or less (OR=1.51, 95% CI=1.16-1.98), being unmarried (OR=1.99, 95% CI=1.58-2.50), annual income less than $20,000 (OR=1.63, 95% CI=1.21-2.20), and being unemployed (OR=2.01, 95% CI=1.62-2.51). Intensive treatment was also associated with increased risk of full PTSD (OR=1.36, 95% CI 1.06 -1.74).
Conclusions
Posttraumatic stress disorder is reported significantly more often by childhood cancer survivors than by sibling controls. Although most survivors are apparently doing well, a subset report significant impairment that may warrant targeted intervention.
doi:10.1542/peds.2009-2308
PMCID: PMC3098501  PMID: 20435702
childhood cancer; young adult
25.  Perceived Positive Impact of Cancer Among Long-term Survivors of Childhood Cancer: a report from the Childhood Cancer Survivor Study 
Psycho-oncology  2011;21(6):630-639.
Background
Investigations examining psychosocial adjustment among childhood cancer survivors have focused primarily on negative effects and psychopathology. Emergent literature suggests the existence of positive impact or adjustment experienced after cancer, as well. The purpose of this study is to examine the distribution of Perceived Positive Impact (PPI) and its correlates in young adult survivors of childhood cancer.
Methods
6,425 survivors and 360 siblings completed a comprehensive health survey, inclusive of a modified version of the Posttraumatic Growth Inventory (PTGI) as a measure of PPI. Linear regression models were used to examine demographic, disease and treatment characteristics associated with PPI.
Results
Survivors were significantly more likely than siblings to report PPI. Endorsement of PPI was significantly greater among female and non-white survivors, and among survivors exposed to at least one intense therapy, a second malignancy or cancer recurrence. Survivors diagnosed at older ages and fewer years since diagnosis were more likely to report PPI. Income, education and marital/relationship status appeared to have varied relationships to PPI depending upon the subscale being evaluated.
Conclusions
The existence and variability of PPI in survivors in this study suggest that individual characteristics, inclusive of race, gender, cancer type, intensity of treatment, age at diagnosis and time since diagnosis, have unique and specific associations with different aspects of perceived positive outcomes of childhood cancer.
doi:10.1002/pon.1959
PMCID: PMC3697081  PMID: 21425388
Psychosocial; childhood cancer; trauma; event centrality; survivors

Results 1-25 (1062641)