Cardiac dysfunction in cancer survivors unmasked during exercise

Introduction: The cardiac dysfunction associated with anthracycline-based chemotherapy cancer treatment can exist sub-clinically for decades before overt presentation. Stress echocardiography, the measurement of left ventricular (LV) deformation and arterial haemodynamic evaluation have separately been used to identify sub-clinical cardiovascular (CV) dysfunction in several patient groups including those with hypertension and diabetes. The purpose of the present cross-sectional study was to determine whether the combination of these techniques could be used to improve the characterisation of sub-clinical CV dysfunction in long-term cancer survivors previously treated with anthracyclines. Materials and methods: Thirteen long-term cancer survivors (36±10 years) with prior anthracycline exposure (11±8 years post-treatment) and 13 age-matched controls were recruited. Left ventricular structure, function and deformation were assessed using echocardiography. Augmentation index was used to quantify arterial haemodynamic load and was measured using applanation tonometry. Measurements were taken at rest and during two stages of low-intensity incremental cycling.Results: At rest, both groups had comparable global LV systolic, diastolic and arterial function (all P>0.05), however longitudinal deformation was significantly lower in cancer survivors (-18±2 v -20±2, P<0.05). During exercise this difference between groups persisted and further differences were uncovered with significantly lower apical circumferential deformation in the cancer survivors (-24±5 v -29±5, -29±5 v 35±8 for first and second stage of exercise respectively, both P<0.05). Conclusion: In contrast to resting echocardiography the measurement of LV deformation at rest and during exercise provides a more comprehensive characterisation of sub-clinical LV dysfunction. Larger studies are required to determine the clinical relevance of these preliminary findings

The Establishment of the Nordic Cardio-Oncology Society

Non peer reviewe

Modifiable risk factors associated with bone deficits in childhood cancer survivors

<p>Abstract</p> <p>Background</p> <p>To determine the prevalence and severity of bone deficits in a cohort of childhood cancer survivors (CCS) compared to a healthy sibling control group, and the modifiable factors associated with bone deficits in CCS.</p> <p>Methods</p> <p>Cross-sectional study of bone health in 319 CCS and 208 healthy sibling controls. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA). Generalized estimating equations were used to compare measures between CCS and controls. Among CCS, multivariable logistic regression was used to evaluate odds ratios for BMD Z-score ≤ -1.</p> <p>Results</p> <p>All subjects were younger than 18 years of age. Average time since treatment was 10.1 years (range 4.3 - 17.8 years). CCS were 3.3 times more likely to have whole body BMD Z-score ≤ -1 than controls (95% CI: 1.4-7.8; p = 0.007) and 1.7 times more likely to have lumbar spine BMD Z-score ≤ -1 than controls (95% CI: 1.0-2.7; p = 0.03). Among CCS, hypogonadism, lower lean body mass, higher daily television/computer screen time, lower physical activity, and higher inflammatory marker IL-6, increased the odds of having a BMD Z-score ≤ -1.</p> <p>Conclusions</p> <p>CCS, less than 18 years of age, have bone deficits compared to a healthy control group. Sedentary lifestyle and inflammation may play a role in bone deficits in CCS. Counseling CCS and their caretakers on decreasing television/computer screen time and increasing activity may improve bone health.</p

Bone Mineral Density Evolution and Its Determinants in Long-term Survivors of Childhood Acute Leukemia A Leucemies Enfants Adolescents Study

This prospective study aimed to analyze determinants that can influence bone mineral density evolution in childhood acute leukemia survivors. Patients included were selected from the long-term follow-up LEA cohort and had dual energy radiograph absorptiometry scan between 10 and 18 years and after the age of 18. All scans were centrally reviewed. Bone mineral density was measured at the lumbar spine, femoral neck, total hip, and whole body, and expressed as z-score. Eighty-nine patients (female 39, lymphoblastic leukemia 68, relapse 25, hematopoietic stem cell transplantation 44, and mean age 15.4 and 20.1 years at the first and second scans, respectively) were studied. The first and second scan z-scores were significantly correlated (P < 10(-3)). Mean femoral neck and total hip z-scores improved significantly between the first and second scans, whereas no significant evolution occurred at the lumbar spine and whole-body level. On the second evaluation, 14.6% of patients had z-score <-2 at the lumbar spine and 4.3% at the femoral neck level. Gender, type of leukemia, transplantation, relapse, cumulative corticosteroid doses, or growth hormone deficiency did not have any significant impact on z-score variation. Younger age at diagnosis (<= 8.5 years) proved an unfavorable risk factor for z-score evolution at the lumbar spine (P = 0.041); the trend did not reach statistical significance for metabolic syndrome (P = 0.054). At the femoral neck, both were associated with unfavorable z-score evolution (P = 0.003 and 0.025, respectively). Patients treated at a younger age and those with metabolic syndrome seem to be at higher risk of bone mineral density decline and should benefit from specific interventions

Pediatric DXA: clinical applications

Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation

Childhood acute lymphoblastic leukaemia. Late effects in young adult survivors

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. The 5-year survival rate has gradually increased from 5% in early 1970s to over 80% today. Until now most patients have been discharged from further follow up after puberty. The general aim of this thesis was to investigate long-term side effects in a homogenous group of young adult survivors of childhood ALL.Thirty-five young adults in the age 20-32 years, who had been treated for ALL before puberty, were investigated. They had all received chemotherapeutic treatment and corticosteroids. Nineteen had received a low dose prophylactic radiotherapy to the central nervous system (18-24 Gy).In spite of little or no effect on final height we found low spontaneous GH secretion during 24-hours in 50% of the cranially irradiated patients. Low serum levels of IGF-I did not identify patients with low GH secretion. One third of the patients were overweight (BMI 25-29.9 kg/m2), but no patient was obese according to WHO criteria (BMI ¡Ý 30 kg/m2). The maximal GH peak correlated to percentage of total body fat, trunk fat and fat free mass. Reduced GH secretion was correlated with unfavourable serum lipid levels. Thirty-seven percent fulfilled one or two criteria for the metabolic syndrome although no patient had the complete syndrome by definition. Bone mineral density (BMD) was slightly reduced in lumbar spine (-0.4 SD). BMD and markers of bone turnover in femoral neck were correlated to physical performance but not to spontaneous GH secretion. Twenty-three patients who all had received anthracyclines in comparably low doses were also investigated with exercise stress echocardiography and compared with 12 healthy controls. The results demonstrated subclinical, left ventricular systolic dysfunction detected at stress, in 50% of the patients. The most marked difference was in ejection fraction at stress; 10 out of 23 patients reduced their ejection fraction at stress compared with at rest; this was not found in any of the controls. Conclusions. In this study with very long follow up in a homogenous cohort of seemingly healthy adult ALL survivors, we found reasons for future follow up. The main findings are risk of GH deficiency in cranially irradiated patients and risk of anthracycline-induced systolic cardiac dysfunction and other metabolic risk factors. Furthermore, we propose that lifestyle education promoting physical activity is encouraged from an early point in time for ALL patients to prevent obesity and impaired bone mineral density

Childhood acute lymphoblastic leukaemia. Late effects in young adult survivors

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. The 5-year survival rate has gradually increased from 5% in early 1970s to over 80% today. Until now most patients have been discharged from further follow up after puberty. The general aim of this thesis was to investigate long-term side effects in a homogenous group of young adult survivors of childhood ALL.Thirty-five young adults in the age 20-32 years, who had been treated for ALL before puberty, were investigated. They had all received chemotherapeutic treatment and corticosteroids. Nineteen had received a low dose prophylactic radiotherapy to the central nervous system (18-24 Gy).In spite of little or no effect on final height we found low spontaneous GH secretion during 24-hours in 50% of the cranially irradiated patients. Low serum levels of IGF-I did not identify patients with low GH secretion. One third of the patients were overweight (BMI 25-29.9 kg/m2), but no patient was obese according to WHO criteria (BMI ¡Ý 30 kg/m2). The maximal GH peak correlated to percentage of total body fat, trunk fat and fat free mass. Reduced GH secretion was correlated with unfavourable serum lipid levels. Thirty-seven percent fulfilled one or two criteria for the metabolic syndrome although no patient had the complete syndrome by definition. Bone mineral density (BMD) was slightly reduced in lumbar spine (-0.4 SD). BMD and markers of bone turnover in femoral neck were correlated to physical performance but not to spontaneous GH secretion. Twenty-three patients who all had received anthracyclines in comparably low doses were also investigated with exercise stress echocardiography and compared with 12 healthy controls. The results demonstrated subclinical, left ventricular systolic dysfunction detected at stress, in 50% of the patients. The most marked difference was in ejection fraction at stress; 10 out of 23 patients reduced their ejection fraction at stress compared with at rest; this was not found in any of the controls. Conclusions. In this study with very long follow up in a homogenous cohort of seemingly healthy adult ALL survivors, we found reasons for future follow up. The main findings are risk of GH deficiency in cranially irradiated patients and risk of anthracycline-induced systolic cardiac dysfunction and other metabolic risk factors. Furthermore, we propose that lifestyle education promoting physical activity is encouraged from an early point in time for ALL patients to prevent obesity and impaired bone mineral density

Young adult survivors of childhood acute lymphoblastic leukemia: spontaneous GH secretion in relation to CNS radiation

BACKGROUND: Young adults who are long-term survivors of acute lymphoblastic leukaemia (ALL) in early childhood usually do well and do not have to go to regular medical checkups. Many of these survivors did receive prophylactic cranial radiotherapy during their oncological treatment. The effect of cranial irradiation on the hypothalamus is considered to be progressive. Therefore, late effects, such as reduced growth hormone (GH) secretion, may remain undetected until adulthood. PROCEDURE: Records from all patients treated for ALL before the onset of puberty in the region of West Sweden, between 1 January 1973 and 31 December 1985 were included, provided they were in first remission with a minimum follow-up time of 15 years, and a minimum age of 20. These criteria were met by 47 young adults aged 20-32 years, of whom 35 agreed to participate. We studied spontaneous GH secretion over 24 hr, IGF-I and IGFBP-3, final height and BMI. The patients had been treated according to three consecutive Swedish childhood leukaemia group protocols. The median follow-up time was 20 years, and 19 of the patients had been treated with cranial irradiation (CRT+), 16 had not (CRT-). RESULTS: CRT+ patients had significantly lower maximal peaks of GH than CRT- patients. Fifty percent of the CRT+ patients had a GH(max) below the cut-off level (3.3 microg/l), for GH treatment. CRT- patients all had GH(max) levels considered within the normal range. Final height of all the patients, except one CRT+ women, was in the range of expected midparental height, the median loss in final height in the CRT+ patients was 0.8 standard deviation (SD). No patient in this study was obese by definition (BMI <30 kg/m(2)). IGF-I and IGFBP-3 concentrations did not correlate to variations in spontaneous GH secretion in these patients. CONCLUSIONS: In spite of the little effect on final height, we found impaired spontaneous GH secretion in 79% of young adults 20-32 years of age, and GH deficiency (GHD) in 47% after low-dose cranial irradiation in early childhood. The consequences of this low-GH secretion need to be investigated