Occurrence Of Late Effects Research Articles

Disparities in the Occurrence of Late Effects following Treatment among Adolescent and Young Adult Melanoma Survivors.

Melanoma is the third most common cancer in the adolescent and young adult (AYA) population; however, no studies have addressed the occurrence of adverse health conditions following melanoma treatment in these survivors. Data for patients ages 15 to 39 years diagnosed with cutaneous melanoma from 1996 to 2012 and surviving ≥2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. The influence of age at diagnosis, sex, race/ethnicity, neighborhood socioeconomic status (SES), health insurance, and surgery on the development of adverse health conditions was evaluated using Cox proportional hazards regression models. Of 8,259 patients, 35.3% were male, 83.3% were non-Hispanic White, 82.4% had private health insurance, and 60.5% were considered high SES. In Cox regression models, males had an increased risk of developing adverse health conditions across all systems, including cardiac [HR, 1.73, 95% confidence interval (CI), 1.47-2.03], lymphedema (HR, 1.56; 95% CI, 1.37-1.77), hematologic disorders (HR, 1.17; 95% CI, 1.03-1.33), major infection/sepsis (HR, 1.59; 95% CI, 1.39-1.82), and second cancers (HR, 1.51; 95% CI, 1.31-1.74). Patients with public/no insurance (vs. private) had a greater risk of developing all studied adverse health conditions, including subsequent cancers (HR, 2.34; 95% CI, 1.94-2.82). AYA patients residing in low SES neighborhoods had similar increased risk of developing adverse health conditions. Of AYA melanoma survivors, males, those with public/no health insurance, and those living in low SES neighborhoods had a greater likelihood of developing adverse health conditions. Strategies to improve surveillance and secondary prevention of these adverse health conditions are needed among AYA melanoma survivors, specifically for the at-risk populations identified.

Chronic medical conditions and late effects following non-Hodgkin lymphoma in HIV-uninfected and HIV-infected adolescents and young adults: a population-based study.

Little is known about the incidence of late effects following non-Hodgkin lymphoma (NHL) among adolescent and young adult (AYA, 15-39years) survivors. Using data from the California Cancer Registry linked to hospital discharge, we estimated the cumulative incidence of late effects at 10years among AYAs diagnosed with NHL during 1996-2012, who survived ≥2years. Cox proportional-hazards models were used to investigate the influence of sociodemographic and clinical factors on the occurrence of late effects. Of 4392 HIV-uninfected patients, the highest incident diseases were: endocrine (18·5%), cardiovascular (11·7%), and respiratory (5·0%), followed by secondary primary malignancy (SPM, 2·6%), renal and neurologic (2·2%), liver/pancreatic (2·0%), and avascular necrosis (1·2%). Among the 425 HIV-infected survivors, incidence was higher for all late effects, especially over threefold increased risk of SPM, compared to HIV-uninfected patients (8·1% vs. 2·6%). In multivariable models for HIV-uninfected patients, public or no health insurance (vs. private), residence in lower socioeconomic neighbourhoods (vs. higher), and receipt of a haematopoietic stem cell transplant were associated with a greater risk of most late effects. Our findings of substantial incidence of late effects among NHL AYA survivors emphasise the need for longterm follow-up and appropriate survivorship care to reduce morbidity and mortality in this vulnerable population.

Disparities in the occurrence of late effects following treatment among adolescent and young adult melanoma survivors.

9580 Background: Melanoma is the third most common cancer in the adolescent and young adult (AYA) population and the incidence worldwide is increasing. However, no studies have addressed the occurrence of late effect medical conditions following melanoma treatment in these young survivors. Methods: All patients ages 15-39 diagnosed with cutaneous melanoma from the 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. The influence of age at diagnosis, sex, race/ethnicity, neighborhood socioeconomic status (SES), and health insurance on the development of late effects by system was evaluated using multivariable Cox proportional hazards regression models. Results: Of 8,524 patients, 35.6% were male, 83.1% non-Hispanic white, 82.1% had private health insurance, 60.3% were considered high SES, and 70.7% had no documented co-morbidities at diagnosis. After controlling for competing factors, males had an increased risk of developing late effects across all systems, including cardiac [HR:2.13, 95%CI 1.87-2.42], neurologic (HR:2.24, CI 1.92-2.63), lymphedema (HR:2.22, CI 1.89-2.62), bleeding events (HR:2.35, CI 2.00-2.77), major infection/sepsis (HR:2.23, CI 1.95-2.56), and second cancers [HR:1.66, CI 1.47-1.89]. In addition, patients with public or no insurance (vs. private) had a greater risk of developing all studied late effects, including lymphedema (HR:2.48, CI 2.04-3.01), respiratory illness (HR:2.21, CI 1.85-2.64) renal dysfunction (HR:2.31, CI 1.90-2.81), and subsequent cancers (HR:1.82, CI 1.54-2.16). AYA patients residing in low SES neighborhoods had a similar increased risk of developing late effects. However, neither age nor race/ethnicity had an impact on the occurrence of late effects. Conclusions: Of AYA melanoma survivors, males, those with public or no health insurance, and those living in low SES neighborhoods had a much greater likelihood of developing of late effects. Strategies to improve surveillance and secondary prevention of these late effects is needed among AYA melanoma survivors, particularly for this demographic.

Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).

LBA2 Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed < 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect late-effects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p < .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p < .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality. [Table: see text]

Late Outcomes of Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL) Diagnosed Between 1963-2002: A Report from the St. Jude Lifetime (SJLIFE) Cohort Study

Introduction: Treatment for childhood ALL has evolved over the last five decades and transformed a once fatal disease to one with 5-year survival rates in excess of 90%. However, aging survivors of ALL are at risk for adverse health and social outcomes that significantly impact overall quality of life. Comprehensive clinical assessments of adults previously treated for childhood ALL are lacking, with most reports relying upon registry or self-reported data. To evaluate the impact of changes in therapy for ALL on the risk of late effects, we systematically screened and clinically assessed the largest cohort to date of adult survivors of childhood ALL treated over the last five decades. Our aim was to determine the occurrence of and risk factors for late chronic health conditions, neurocognitive deficits, and physical function limitations.Methods: History/physical examination, laboratory analysis, neurocognitive testing, and physical fitness were assessed among 934 (65.7% of eligible) survivors of pediatric ALL ≥ 18 years of age, treated at St. Jude Children’s Research Hospital ≥ 10 years ago, and participating in the SJLIFE cohort study. Chronic health conditions were graded per CTCAE criteria (v4.03). Neurocognitive function was measured in the domains of attention and executive function using standard clinical tests. Using national norms, age-adjusted z-scores were calculated. Mild impairment was defined as a z-score between -1 to -2, severe as ≤ -2. Aerobic function was measured with the 6-minute walk test [6MWT] (abnormal ≤ 490 meters) and mobility by the timed up and go test [TUG] (abnormal > 6 seconds to rise from a chair, walk 3 meters, return, and sit). Log-binomial linear models were used to evaluate relative risk (RR) and 95% confidence intervals (CI) for associations between treatment and outcome.Results: Survivors (50% female, 90% white) had a median age at diagnosis of 5.1 years (range 0.2-19.5), 31.2 years (18.4-59.7) at evaluation, and were 25.0 years (10.5-47.7) from diagnosis. Three hundred twenty-one (34.4%) received ≥ 24 Gy cranial radiation (CRT), 224 (24%) < 24 Gy, and 389 (41.6%) no CRT, of whom 373 were treated with high dose methotrexate (HDMTX). Nearly the entire cohort had at least one chronic condition (98%) and 59% a severe/life-threating condition (grades 3-4). The most common were obesity (70%), hypertension (70%), and peripheral sensory neuropathy (51.6%). Chronic conditions were more common in males (52% vs. 48%, p=0.003). By age 40, the cumulative prevalence of at least one chronic condition was 90% and 69% for a severe/life-threatening condition. After adjusting for age at diagnosis, age at evaluation, and gender, survivors exposed to CRT were more likely to have a severe/life-threatening condition (RR 1.3 95% CI 1.1-1.5) than those not exposed to CRT. One hundred sixty-eight survivors had 228 second neoplasms (121 malignant [79 non-melanoma skin cancers], 107 benign). Attention and executive function deficits (mild and severe) were identified across each category of CNS directed therapy (≥ 24 Gy CRT, < 24 Gy CRT, HDMTX) [table]. After adjustment for age at diagnosis and gender, those treated with CRT only were more likely to have mild (RR 1.4 95% CI 1.0-1.9) and severe (RR 2.2 95% CI 1.7-3.0) attention and executive function (RR 1.4 95% CI 1.1-1.8, RR 1.7 95% CI 1.4-2.2) deficits compared to those treated with HDMTX. Abnormal 6MWT was identified among 20.5% of the ALL survivors, 26.7% of those treated with CRT and 15.1% HDMTX. TUGS was abnormal in 35.5% of the cohort, 41.6% treated with CRT, 27.3% HDMTX. Adjusting for age at diagnosis, age at evaluation, gender, BMI, and educational attainment, CRT was significantly associated with impaired 6MWT (RR 1.8 95% CI 1.1-2.9) but not TUGS (RR 1.1 95% CI 0.9-1.4).Conclusions: Systematic evaluation identified a substantial number of medical conditions, deficits in attention and executive function, and functional impairments in adult survivors of childhood ALL at a young age. Removal of CRT has significantly reduced, but not eliminated, the occurrence of late effects. Maintaining health and quality of life in this population requires significant medical surveillance, counseling, and lifestyle modifications.TableCNS Directed ThreapyNeurocognitive Deficit≥ 24 Gy< 24 GyHDMTXAttentionMild19.3%20.6%17.1%Severe31.6%22.8%14.1%Executive FunctionMild28.3%28.2%24.4%Severe35.4%24.1%20.3% DisclosuresNo relevant conflicts of interest to declare.

Health-Related Quality of Life of Young Adult Survivors of Childhood Cancer: A Review of Qualitative Studies.

Purpose: The occurrence of late effects, combined with traditional growth and developmental issues, can significantly affect the health-related quality of life (HRQOL) of young adult survivors of childhood cancer (YASCC). Limited HRQOL measurement tools have been developed or validated for YASCC. The purpose of this study was to identify the domains of HRQOL that are unique to YASCC by conducting a systematic review of qualitative studies. Specifically, we compared the findings to the classical framework of HRQOL that was developed for survivors of adult-onset cancer and identified specific domains not being assessed in existing HRQOL instruments for YASCC. Methods: We searched qualitative studies published in peer-reviewed journals from 2000 to 2010 in the PsychINFO, PubMed, and EBSCOhost databases. A set of keywords and inclusion/exclusion criteria were utilized to identify eligible studies with a focus on survivorship and HRQOL issues of YASCC. Results: Sixteen studies met the inclusion/exclusion criteria and were investigated in this study. Six important domains of HRQOL were identified (physical, social, psychological, spiritual, fertility/sexual, resilience, and body appearance) with several sub-domains. Conclusion: Use of the classical HRQOL framework and existing instruments is not comprehensive enough for YASCC. Adding unique domains to the classical framework and existing instruments will make them valuable tools for measuring the HRQOL of YASCC and increase health professionals' ability to identify if and when psychosocial services are needed for this unique population.

Plankton stress responses from PAH exposure and nutrient enrichment

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 363:121-130 (2008) - DOI: https://doi.org/10.3354/meps07470 Plankton stress responses from PAH exposure and nutrient enrichment M. Hjorth1,2,*, V. E. Forbes2, I. Dahllöf1 1Department of Marine Ecology, National Environmental Research Institute, University of Aarhus, Frederiksborgvej 399, 4000 Roskilde, Denmark 2Department of Environmental, Social and Spatial Change, Roskilde University, Universitetsvej 1, 4000 Roskilde, Denmark *Email: moh@dmu.dk ABSTRACT: The hypothesis that the nature and force of PAH stress responses from plankton systems are coupled to the nutrient status of that system was tested in a mesocosm experiment. Four treatments were applied consisting of control (Cn), pyrene exposed (Py), nutrient spiked (Nu), and nutrient spiked and pyrene exposed (NuPy) groups in replicate bags (n = 3) representing plankton communities including bacteria, phytoplankton and zooplankton. Regardless of nutrient status, all the Py mesocosms were affected directly with decreases in chlorophyll a concentrations to 20% of control values on Day 1. Primary production was also significantly lower (<50%) than Cn communities in both Py and NuPy communities after the first pyrene exposure. Indirect effects were observed as increased bacterial activity due to nutrient release from algal death, thereby channelling growth to another trophic level. With time the plankton system became top-down controlled, dominated by zooplankton, which was also the trophic group experiencing the longest lasting effect on structure. The occurrence of late effects in the zooplankton communities were seen in all treatments, but the magnitude of the effects was dependent on the nutrient status, most probably because of a larger trophic transfer of the contaminant. To improve our understanding of contaminant effects on food webs in natural communities, it is imperative that interactions between trophic levels in relation to abiotic factors are investigated. KEY WORDS: Plankton · PAH · Food web · Stress · Function · Nutrient status · Marine · Mesocosm Full text in pdf format PreviousNextCite this article as: Hjorth M, Forbes VE, Dahllöf I (2008) Plankton stress responses from PAH exposure and nutrient enrichment. Mar Ecol Prog Ser 363:121-130. https://doi.org/10.3354/meps07470 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 363. Online publication date: July 15, 2008 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2008 Inter-Research.

Increased late toxicity in 12–20 year survivors of germ cell tumors (GCT)

4509 Background: There is extensive literature on occurrence of late effects of cisplatin-based chemotherapy, but it comes from centers of excellence and may reflect case selection or ascertainment biases. Funded by the NIH SEER Program and the Lance Armstrong Foundation, we studied community-based late outcomes via identification of cases from the Los Angeles SEER Tumor Registry and comparison with a control group. Methods: We identified 951 patients treated in Los Angeles County through the records of the L.A. SEER Cancer Registry/Cancer Surveillance Program (CSP) for 1983–1987, giving a minimum follow-up of 12 years. Consent was obtained from physician of record and forms sent to the patients, requesting information about a broad range of demographic, treatment-related and psycho-social issues. In addition, patients were asked to provide a “control”, a friend of approximately the same age at time of diagnosis, known to the patient before diagnosis and known not to have a history of testis cancer. Questionnaires were also sent to controls, to allow data comparison with patients. Anticipated initial difficulties included mobility of young males and invalid addresses. This occurred in &gt; 50% of cases, and we used a planned strategy for acquisition through State agencies, Department of Motor Vehicles, etc. Results: Surveys were returned by 298 cases and 67 control subjects, and 35 patients refused. In 1983–87, success rates were lower, and 142 patients had died. An unexpected problem was reluctance or inability of subjects to identify friends of comparable age to provide a control population. Differences in groups are summarized in the Table. Conclusions: Long term survivors with GCT have an excess of late toxicity, including cardiovascular, neurological, hematologic, musculoskeletal and neoplastic problems, which increase with time. These data should assist in design of surveillance protocols. [Table: see text] No significant financial relationships to disclose.

Quantification of late complications after radiation therapy

Abstract Background : An increasing number of patients survive cancer after having received radiation therapy. Therefore, the occurrence of late normal tissue complications among long-term survivors is of particular concern. Methods : Sixty-three patients treated by radical surgery and irradiation for rectal carcinoma were subjected to an unconventional sandwich therapy. Preoperative irradiation was given in four fractions of 5 Gy each applied within 2 or 3 days; postoperative irradiation consisted mostly of 15×2 Gy (range, 20–40 Gy). A considerable proportion of these patients developed severe late complications (Radiother Oncol 53 (1999) 177). The data allowed a detailed analysis of complication kinetics, leading to a new model which was tested using data from the literature. Results : Data on late complications were obtained for eight different organs with a follow-up of up to 10 years. For the various organs, the percentage of patients being free from late complications, plotted as a function of time after start of radiation therapy, was adequately described by exponential regression. From the fit, the parameter p a was obtained, which is the percentage of patients at risk in a given year of developing a complication in a given organ during that year. The rate p a remained about constant with time. Following sandwich therapy, the annual incidence of complications in the bladder, ileum, lymphatic and soft tissue, and ureters was about the same ( p a =10–14%/year), whereas complications in bone or dermis occurred at lower rates (4.7 or 7.5%/year, respectively). Discussion : Numerous data sets collected from published reports were analyzed in the same way. Many of the data sets studied were from patients in a series where there was a high incidence of late effects. Three types of kinetics for the occurrence of late effects after radiotherapy were identified: Type 1, purely exponential kinetics; Type 2, exponential kinetics, the slope of which decreased exponentially with time; Type 3, curves composed of two components, a fast initial decline followed by an exponential decrease. For each kind of kinetics, provided that the dose distribution is not too heterogeneous, the incidence of late effects appears to occur at exponential or approximately exponential kinetics, even many years after treatment. This implies that a random process might be involved in the occurrence of late radiation sequelae. Conclusions : There might be a lifelong risk of developing late complications, of which patients and clinicians should be aware. It appears worthwhile to try to identify, in follow-up examinations of patients after radiation therapy, what kind of processes might be involved in triggering subclinical residual injury to develop into a clinically manifest late effect.

Issues in the consideration of intervention strategies in long-term survivors of childhood cancer.

With the improved survival of children with cancer, increased attention is being focused on the health status of survivors. The ultimate objective of this research is to use the results to design and test rational intervention strategies directed toward reduction of morbidity and mortality associated with the diagnosis and successful treatment of cancer. After treatment and patient characteristics that confer a high risk for adverse sequelae are identified, intervention programs targeting primary or secondary interventions must be actively pursued. Primary interventions would include modifications to cancer treatment protocols to maintain a high degree of effectiveness but reduce the occurrence of late effects. Opportunities exist for secondary intervention research in a number of areas, including second cancers (smoking cessation/prevention, early detection, chemoprevention), cardiopulmonary dysfunction (diagnosis and treatment of comorbid disease and promotion of healthy life style practices), and reproduction/genetic risks (management, counseling, networking). It is likely that testing of intervention strategies will require collaborative studies involving a multidisciplinary team of investigators and a multi-institutional structure for access to a suitable survivor population.

Coping with a Second Disability: Implications of the Late Effects of Poliomyelitis for Occupational Therapists

The long term effects of many physical disabilities have only recently begun to be appreciated. For people who have lived for years with what they thought to be stable conditions, the onset of secondary disabilities may be associated with considerable problems and distress. A questionnaire survey of 324 people with poliomyelitis revealed the occurrence of late effects in 94% of respondents. The majority reported increased weakness, pain and fatigue, problems in carrying out daily living activities and difficulties in obtaining appropriate health care. Although occupational therapists were less likely to be consulted than other professionals, they received one of the highest satisfaction ratings from clients. Discussion of case studies indicates ways in which occupational therapists can provide symptom relief and enable clients to maintain valued roles. As the survival rates of people with disabilities increase there is a need for greater awareness of, and research into, the late effects of disability.