Relevance of historical therapeutic approaches to the contemporary treatment of pediatric solid tumors
Departments of Epidemiology and Cancer Control, St. Jude Children's Research Hospital Memphis, Memphis, Tennessee. .Pediatric Blood & Cancer (Impact Factor: 2.39). 07/2013; 60(7). DOI: 10.1002/pbc.24487
Children with solid tumors, most of which are malignant, have an excellent prognosis when treated on contemporary regimens. These regimens, which incorporate chemotherapeutic agents and treatment modalities used for many decades, have evolved to improve relapse-free survival and reduce long-term toxicity. This review discusses the evolution of the treatment regimens employed for management of the most common solid tumors, emphasizing the similarities between contemporary and historical regimens. These similarities allow the use of historical patient cohorts to identify the late effects of successful therapy and to evaluate remedial interventions for these adverse effects. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
- [Show abstract] [Hide abstract]
ABSTRACT: Adult survivors of childhood cancer are known to be at risk for treatment-related adverse health outcomes. A large population of survivors has not been evaluated using a comprehensive systematic clinical assessment to determine the prevalence of chronic health conditions. To determine the prevalence of adverse health outcomes and the proportion associated with treatment-related exposures in a large cohort of adult survivors of childhood cancer. Presence of health outcomes was ascertained using systematic exposure-based medical assessments among 1713 adult (median age, 32 [range, 18-60] years) survivors of childhood cancer (median time from diagnosis, 25 [range, 10-47] years) enrolled in the St Jude Lifetime Cohort Study since October 1, 2007, and undergoing follow-up through October 31, 2012. MAIN OUTCOMES AND MEASURES: Age-specific cumulative prevalence of adverse outcomes by organ system. Using clinical criteria, the crude prevalence of adverse health outcomes was highest for pulmonary (abnormal pulmonary function, 65.2% [95% CI, 60.4%-69.8%]), auditory (hearing loss, 62.1% [95% CI, 55.8%-68.2%]), endocrine or reproductive (any endocrine condition, such as hypothalamic-pituitary axis disorders and male germ cell dysfunction, 62.0% [95% CI, 59.5%-64.6%]), cardiac (any cardiac condition, such as heart valve disorders, 56.4% [95% CI, 53.5%-59.2%]), and neurocognitive (neurocognitive impairment, 48.0% [95% CI, 44.9%-51.0%]) function, whereas abnormalities involving hepatic (liver dysfunction, 13.0% [95% CI, 10.8%-15.3%]), skeletal (osteoporosis, 9.6% [95% CI, 8.0%-11.5%]), renal (kidney dysfunction, 5.0% [95% CI, 4.0%-6.3%]), and hematopoietic (abnormal blood cell counts, 3.0% [95% CI, 2.1%-3.9%]) function were less common. Among survivors at risk for adverse outcomes following specific cancer treatment modalities, the estimated cumulative prevalence at age 50 years was 21.6% (95% CI, 19.3%-23.9%) for cardiomyopathy, 83.5% (95% CI, 80.2%-86.8%) for heart valve disorder, 81.3% (95% CI, 77.6%-85.0%) for pulmonary dysfunction, 76.8% (95% CI, 73.6%-80.0%) for pituitary dysfunction, 86.5% (95% CI, 82.3%-90.7%) for hearing loss, 31.9% (95% CI, 28.0%-35.8%) for primary ovarian failure, 31.1% (95% CI, 27.3%-34.9%) for Leydig cell failure, and 40.9% (95% CI, 32.0%-49.8%) for breast cancer. At age 45 years, the estimated cumulative prevalence of any chronic health condition was 95.5% (95% CI, 94.8%-98.6%) and 80.5% (95% CI, 73.0%-86.6%) for a serious/disabling or life-threatening chronic condition. Among adult survivors of childhood cancer, the prevalence of adverse health outcomes was high, and a systematic risk-based medical assessment identified a substantial number of previously undiagnosed problems that are more prevalent in an older population. These findings underscore the importance of ongoing health monitoring for adults who survive childhood cancer.JAMA The Journal of the American Medical Association 06/2013; 309(22):2371-81. DOI:10.1001/jama.2013.6296 · 35.29 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background: Childhood cancer survivors (CCS) are more insulin resistant (IR) and have higher levels of several cardiovascular (CV) risk factors even while still children. This study examines specific treatment exposures associated with CV risk factors and IR. Methods: CCS age 9-18 years at study entry and in remission >5 years from diagnosis (n=319) and 208 sibling controls were recruited into this cross-sectional study that included physiologic assessment of IR (hyperinsulinemic euglycemic clamp) and assessment of CV risk factors.. Regression and recursive tree modeling were used to ascertain treatment combinations associated with IR and CV risk. Results: Mean current age of CCS was 14.5yr, 54% were male (siblings 13.6yr, 54% male). Diagnoses included leukemia (35%), brain tumors (36%), solid tumors (33%) or lymphoma (6%). Among CCS, analysis of individual chemotherapy agents failed to find associations with CV risk factors or IR. Compared to siblings, IR was significantly higher in CCS who received platinum plus cranial radiation (CRT, 92% brain tumors) and in those who received steroids but no platinum (majority leukemia). IR did not differ between CCS who received surgery alone vs. siblings. Within survivor comparisons failed to elucidate treatment combinations that increased IR compared to those who received surgery only. Conclusions: Exposure to platinum, CRT or steroids is associated with IR and CV risk factors and should be taken into consideration in the development of screening recommendations for CV risk. Impact: Earlier identification of CCS who may benefit from targeted prevention efforts may reduce their future risk of CV disease.Cancer Epidemiology Biomarkers & Prevention 09/2013; 22(11). DOI:10.1158/1055-9965.EPI-13-0610 · 4.13 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Background/aims: The substantial improvement in survival of children with cancer has been achieved at the cost of late effects. We aimed to evaluate the endocrine outcome in survivors of childhood non-brain malignant solid tumors (NBMST). Methods: We performed a retrospective medical record review for medical history, clinical and laboratory data of survivors (n = 139) followed at the endocrine clinic of a tertiary medical center. Outcome measures were frequency and types of endocrine dysfunction and components of the metabolic syndrome. Results: Median follow-up time was 9.0 years (range 1.2-29.5 years). At least one endocrine abnormality was found in 44 patients (31.7%). Abnormalities included hypogonadism (11.5%), hypothyroidism (9.4%), short stature (9.4%), growth hormone deficiency (8.6%) and components of the metabolic syndrome (15.1%). Height SDS decreased significantly (p = 0.004) during follow-up, whereas body mass index SDS tended to increase. On logistic regression analysis, treatment with cranial irradiation (p = 0.003), local radiation (p = 0.042), or bone marrow transplantation (p = 0.0001), and older age at last visit (p < 0.001) were associated with a significantly higher hazard of an endocrinopathy. Conclusions: The high rate of late endocrine dysfunction among survivors of childhood NBMST highlights the need to optimize the follow-up at the late-effects clinics to identify endocrine problems and allow early and effective intervention.Hormone Research in Paediatrics 11/2013; 81(1). DOI:10.1159/000355577 · 1.57 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.