Bone-mineral density deficits from childhood cancer and its therapy. A review of at-risk patient cohorts and available imaging methods

The growing population of childhood cancer survivors--currently estimated at 1 in 900 young adults aged 15-45 years--underscores the importance of studying long-term complications of oncotherapy. While these patients are returning to the mainstream of life, they carry with them toxicities from prior therapy that may compound or potentiate changes typically seen with the normal aging process. Skeletal toxicities such as scoliosis, craniofacial dysplasia, and limb-length discrepancy are readily apparent. However, others such as osteoporosis and osteonecrosis are silent until they reach advanced stages when attempts at amelioration may be unsuccessful. This review addresses bone-mineral density deficits that may predispose childhood cancer survivors to earlier onset and more severe osteopenia and osteoporosis than the normal population.     

Issues specific to implementing PET–CT for pediatric oncology: what we have learned along the way

In parallel with the expansion of PET imaging to pediatric patients has been the technological development of merging state-of-the-art cross-sectional anatomic information (CT) with functional imaging (PET) into a single modality: PET–CT. Attending to the clinical, scheduling, and medical needs that are unique to imaging children and adolescents can be a challenge, particularly when instituting a single new modality. When that modality bridges two unique, previously independent methods—often previously located in two separate departmental divisions—the details and logistics required to set up a smoothly functioning process can be particularly difficult. This paper focuses on our experience in implementing PET–CT in a tertiary pediatric referral center.Supported in part by grants P30 CA-21765 and P01 CA-20180 from the National Cancer Institute, a Center of Excellence grant from the state of Tennessee from the National Institutes of Health, and by the American Lebanese Syrian Associated Charities (ALSAC)CME activity Please find the CME information and questions at the end of this issueThe author(s) have no financial interest, arrangement, or affiliation to disclose in the context of this CME activity. There is nothing to disclose regarding investigational or off-label use of medical devices or other products, or any pharmaceutical agents     

Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Children's Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Children's Oncology group long-term follow-up guidelines.     

Host factors and consequence of chemotherapy in pediatric cancer patients

The 5-year survival rates for childhood ALL are approaching 80%, but therapy-related toxicities are common. One of the challenges in this population is determining the most efficacious therapeutic regimens for these individuals. Factors such as drug metabolism, genetics, and concomitant disease affect drug efficacy and may be important in determining therapeutic outcomes in these patients. This review will focus on these factors in the treatment of childhood ALL.     

Late effects in childhood cancer survivors: A review with a framing effect bias?

Most publications report the adverse (negative) health issues in childhood cancer survivors. Presenting information to the newly diagnosed patient in a positive manner is advocated, while noting that recurrence is the most likely adverse event. Re‐analysis of population‐based studies on life‐threatening toxicities from Nordic, Dutch, United Kingdom, French, Italian, and N. American publications shows that 5‐year survivors have a near normal life expectancy, 75% have no severe or life‐threatening treatment related toxicity and 87% remain free of a second malignancy. Children who received radiation or anthracycline >250–300 mg/m² are at greatest risk for treatment related life‐threatening toxicities. Pediatr Blood Cancer 2011; 57: 1100–1103. © 2011 Wiley Periodicals, Inc.     

Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults,with emphasis on MRI

Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family.This study was supported in part by grants P30 CA-21765 and P01 CA20180 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC)     

Postoperative small-bowel intussusception in children with cancer

The clinical and imaging features of small-bowel intussusception as a complication of abdominal surgery are not well known. Diagnosis may be delayed because symptoms mimic common postoperative complaints. In pediatric cancer patients, the side effects of chemotherapy and symptoms related to the primary malignancy may also obscure the diagnosis. We report the clinical and radiographic features of eight children undergoing evaluation and treatment for solid tumors who developed small-bowel intussusception following laparotomy. These children represent 2.2% of all children and adolescents who underwent laparotomy at a pediatric cancer research and treatment center during a 13-year period. With prompt diagnosis and intervention, morbidity and mortality from this rare but lifethreatening postoperative complication can be avoided.Supported in part by National Cancer Institute Cancer Center Support grant P30 CA-21765, and by the American Lebanese Syrian Associated Charities (ALSAC)     

Passive smoking: A danger to children''s health

The most common cause of illness in infancy and childhood is acute infection of the respiratory tract. Several recent studies have reported that life-threatening respiratory disease in infancy, such as pneumonia and bronchiolitis, is directly related to the smoking habits of parents. The effects of smoking are more hazardous to youngsters because babies and young children breathe more rapidly than adults. Because of this higher breathing rate, they inhale more air—and more pollution—in comparison to their total body weight. The harmful effects of cigarette smoking on infants and children and recommendations for specific interventions to minimize or eliminate this health hazard are discussed.     

Models of care for survivors of childhood cancer

With improvements in therapy for childhood cancer, the expectation that most childhood cancer patients will survive and enter adulthood is a reality. There is clear evidence that survivors are at risk for adverse health-related long-term sequelae associated with their cancer and its treatment, requiring appropriate health care resources. What is less clear is how this health care should optimally be delivered. We review the functional and operational needs for long-term follow-up for childhood cancer survivors and present alternatives for models of care. Programs for childhood cancer survivors should provide mechanisms for monitoring and management of late effects, as well as support and advocacy for addressing psychosocial issues, health education, and assistance with financial concerns. Access to research is an important component as clinical care and research are integrally related. A multidisciplinary model that provides continuity of care throughout the disease course is optimal, providing transitions from acute anti-neoplastic therapy to follow-up and primary care, as well as from pediatric care to adult-oriented care. There is no single best model of care for all childhood cancer survivors. In evaluating different models, considerations include available resources as well as the particular cancer population being served. Not all survivors require the same level of services and the service level requirement for individual patients may change with time. As outcome research progresses for childhood cancer survivors, methodological issues of optimal health care delivery for this population deserve to be the subject of such research.     

Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group

Curative therapy for childhood cancer has improved significantly in the last 2 decades such that, at present, approximately 80% of all children with cancer are likely to survive > or = 5 years after diagnosis. Prevention, early diagnosis, and treatment of long-term sequelae of therapy have become increasingly more significant as survival rates continue to improve. Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer. The Children's Oncology Group Late Effects Committee and Nursing Discipline and Patient Advocacy Committee have recently developed guidelines for follow-up of long-term survivors of pediatric cancer. A multidisciplinary task force critically reviewed the existing literature to evaluate the evidence for the cardiovascular screening recommended by the Children's Oncology Group guidelines. In this review we outline the clinical manifestations of late cardiovascular toxicities, suggest modalities and frequency of monitoring, and address some of the controversial and unresolved issues regarding cardiovascular disease in childhood cancer survivors.     

Osteoporosis in childhood: bone density of children in health and disease

Bone mineral density in later life largely depends on the peak bone mass achieved in adolescence or young adulthood. A reduced bone density is associated with increased fracture risk in adults as well as in children. Pediatricians should therefore play an important role in the early recognition and treatment of childhood osteoporosis. Juvenile idiopathic osteoporosis and osteogenesis imperfecta are examples of primary osteoporosis in childhood. However, osteoporosis is more frequently a complication of a chronic disease or its treatment. This paper provides an overview of bone and bone metabolism in healthy children and the use of diagnostic tools, such as biochemical markers of bone turnover and several bone densitometry techniques. Furthermore, a number of diseases associated with osteoporosis in childhood and possible treatment strategies are discussed.     

Anterior intervertebral disc herniations in children Report of four cases

Four boys with anterior lumbar disc herniations probably secondary to chronic trauma are reported. Anterior disc herniations may appear as separate lesions — as in our patients — or coexist with Scheuermann's disease. Although Scheuermann's disease, discitis and tuberculosis are regarded as the most common causes of intervertebral disc lesions in childhood, trauma should be excluded as a possible cause in all children with chronic back pain who show localised radiographic signs of narrowed disc spaces with erosive and sclerotic changes in the adjacent vertebrae. Localised mild platyspondyly may be the result of abnormal, prolonged stress and early osteoarthritic changes are to be expected.Presented at the 14th Meeting of the European Society of Pediatric Radiology, Luzern, Switzerland, May 12–14th, 1977, and at the 28 Annual General and Scientific Meeting of the Royal Australian College of Radiologists, Gold Coast, Australia, Sept. 16–20th, 1977     

Incidence of Childhood Cancers in Golestan Province of Iran

Objective

This paper presents the incidence rates of childhood cancers using the data obtained from Golestan population based cancer registry (GPCR) between 2004 and 2006.

Methods

GPCR registers only primary cancers based on standard protocols of the international association of cancer registries (IACR). We collect data on newly diagnosed (incident) cancer cases from all public and private diagnostic and therapeutic centers of the whole province. CanReg-4 software was used for data entry and analysis.

Findings

Totally 5076 cancer cases (all ages) were diagnosed in GPCR between 2004 and 2006. Of these, 139 (2.74 %) were children (aged 0–14 years) with mean (±SD) age of 8.06 (±4.48) years. The age standardized incidence rates for childhood cancer were 119.8 and 78.3 per 1000000 person-years in male and female children, respectively. Leukemia was the most common childhood cancer in Golestan province of Iran. Lymphomas and central nervous system tumors were the second and third ones, respectively.

Conclusion

The incidence rates of childhood cancers were relatively high in Golestan province of Iran. So, controlling of childhood cancers should be mentioned as an important issue in health policy making in this area.     

Children's Oncology Group's 2013 blueprint for research: Epidemiology

Investigators worldwide have for over 40 years conducted case–control studies aimed at determining the causes of childhood cancer. The central challenge to conducting such research is the rarity of childhood cancer, thus many studies aggregate cases through clinical trials organizations such as COG. Rarity also precludes the use of prospective study designs, which are less prone to recall and selection biases. Despite these challenges a substantial literature on childhood cancer etiology has emerged but few strong environmental risk factors have been identified. Genetic studies are thus now coming to the fore with some success. The ultimate aim of epidemiologic studies is to reduce the population burden of childhood cancer by suggesting preventive measures or possibly by enabling early detection. Pediatr Blood Cancer 2013; 60: 1059–1062. © 2012 Wiley Periodicals, Inc.     

Vaccine recommendations for children and youth for the 2014/2015 influenza season

The Canadian Paediatric Society continues to encourage annual influenza vaccination for ALL children and youth ≥6 months of age. Recommendations from the National Advisory Committee on Immunization for the 2014/2015 influenza season include some important changes:

1. Influenza vaccination is recommended for ALL individuals ≥6 months of age, with particular focus on those at high risk of influenza-related complications and their close contacts. Definitions of high-risk conditions and close contacts have not changed from those of 2013/2014.
2. The preference for intranasal, live attenuated influenza vaccine (LAIV) over trivalent inactivated influenza vaccines for healthy children is restricted to individuals two to six years of age. There is insufficient evidence to recommend LAIV over trivalent inactivated influenza vaccines in older children or in children with chronic health conditions; either vaccine may be used unless there are specific contraindications.
3. Quadrivalent influenza vaccines are expected to be available for the 2014/2015 season and may be used interchangeably with trivalent vaccines. They may offer improved protection.
4. Trivalent or quadrivalent inactivated vaccines may be used in individuals with egg allergy; LAIV has not yet been evaluated in this population and is not recommended at this time.

     

IS THE TREATMENT FOR CHILDHOOD SOLID TUMORS ASSOCIATED WITH LOWER BONE MASS THAN THAT FOR LEUKEMIA AND HODGKIN DISEASE?

Background: Cancer disease and its therapy (e.g., chemotherapeutic agents such as glucocorticoids, methotrexate, antymetabolities, cranial and local irradiation) may severely disturb normal growth, bone mineral acquisition, and skeletal development because most individuals go through the stages of rapid growth when childhood cancer is diagnosed. Procedures: To identify factors associated with reduced bone mineral density (BMD) in survivors of childhood cancer the authors examined 114 patients (70 males) who had been treated for acute lymphoblastic leukemia (ALL; n = 43), Hodgkin disease (HD; n = 35), and solid tumors (ST; n = 36) twice. Median age at diagnosis was 8.4 years; at the consecutive examinations it was 12.8 and 16.3 years, respectively. To assess bone density we used dual-energy x-ray absorptiometry (DXA). Results: In the first examination, patients with a history of steroid therapy had higher total and spine BMD and higher BMI (body mass index) than those who were not given steroids. At the end of the follow-up, no differences were found in BMD between subgroups, although BMI was still higher in both ALL and HD patients than in those with ST. Conclusions: Patients treated for solid tumors have reduced bone mass. Low BMI and local irradiation seem to be the factors responsible for reduced BMD in children treated for ST. The use of steroids does not disturb bone mass accumulation in patients treated for childhood malignancies. However, a long-term effect of cancer treatment on osteoporosis risk remains to be determined.     

Cross-sectional study of bone mineral density in adult survivors of solid pediatric cancers

To investigate the hypothesis that survivors of pediatric solid cancer have low bone mineral density, a cross-sectional study was done of subjects who had received treatment for pediatric solid tumors before 16 years of age and were less than 40 years old at follow-up. Excluded were subjects treated for acute lymphoblastic leukemia or those who had received cranial irradiation, total body radiation, or nonautologous bone marrow transplant. The study group consisted of 38 subjects, with the most common diagnoses being lymphoma (n = 17), sarcoma (n = 8), Wilms tumor (n = 5), and neuroblastoma (n = 4). Median age was 22 years (range 12-32). Time from diagnosis of underlying cancer averaged 12.6 years (range 5.5-20.3). Using criteria of osteopenia (Z-score < or = -1.0 and > -2.0) and osteoporosis (Z-score < or = -2.0) for any one or more areas including total body, lumbar spine, total hip, or femoral neck density, 13 of the 38 subjects (34%) had osteopenia or osteoporosis. A further six subjects (16%) had isolated upper extremity osteopenia or osteoporosis. Multivariate analysis showed a direct relationship between the number of chemotherapy drugs administered and the presence of osteopenia or osteoporosis in the lower extremities (P = 0.03). Young survivors of childhood solid tumors are at increased risk of developing premature osteopenia or osteoporosis, and screening evaluations and follow-up are warranted.     

Cancer incidence and survival among children and adolescents in Israel during the years 1998 to 2007

Our goal was to describe childhood cancer incidence and survival in Israel and to identify demographic and epidemiologic variations among children and adolescents with cancer. We used data from the Israel National Cancer Registry to examine the incidence and survival of pediatric cancer in Israeli children aged 0 to 19 years, diagnosed during the years 1998 to 2007. Cases were analyzed according to sex, age, ethnicity, and geographic region. Among the 4255 cases of childhood cancer, there was a total age-adjusted incidence rate of 172.4 per million for children aged 0 to 19 years and 153.4 per million for children aged 0 to 14 years. The incidence rate for boys was higher than for girls (192.5 and 153.3, respectively) and higher for Jewish children than for Arab children (177.6 and 156.8, respectively). The largest groups were leukemias (22%), lymphomas (20.2%), and central nervous system tumors (17.4%). The number of new cases increased each year, but the incidence rate remained steady. The survival probability updated to December 2008 was estimated and the 5-year survival was calculated for the new cases until the end of 2003. The overall survival at 5 years was 80.8%, with 72.8% for the Arabic population and 83.2% for the Jewish population, and depended on the diagnosis. Incidence and survival in childhood cancer in Israel is at the same medium level compared with other parts of the world. This study may set the basis for investigating the genetic and environmental factors that cause pediatric cancer in Israel, delineating the genetic basis for ethnic origin disparities in survival.     

Normal ovarian function and assessment of ovarian reserve in the survivor of childhood cancer

Increasingly young people survive cancer in childhood and as a result complications of its treatment are becoming more common and important. Premature ovarian failure is recognized as a complication of radiotherapy to a field that includes the pelvis and alkylating‐agent‐based chemotherapy. Young pre‐pubertal girls are not protected from the effects of gonadal toxic therapy. A young woman, successfully treated for cancer during childhood, may experience regular periods in the presence of a significantly reduced ovarian reserve. There is, however, no reliable measure of ovarian reserve available for the individual woman. Assessment of ovarian function relies on the use of surrogate markers such as follicle stimulating hormone, inhibin‐B, and anti‐mullerian hormone as well as ultrasound assessment of ovarian volume and antral follicle count. We discuss the physiology of normal ovarian function, the effects of cancer treatments on ovarian function and the techniques for evaluation of ovarian reserve in survivors of childhood cancer. Pediatr Blood Cancer 2009;53:296–302. © 2009 Wiley‐Liss, Inc.     

Mediastinal masses masquerading as common respiratory conditions of childhood: a case series

Introduction  

Leukaemia and lymphoma may present with symptoms and signs mimicking common respiratory conditions of childhood such as asthma or croup. The UK National Institute for Clinical Excellence guidelines for referral for suspected cancer state that “the primary healthcare professional should be ready to review the initial diagnosis in patients in whom common symptoms do not resolve as expected” and “must be alert to the possibility of cancer when confronted by unusual symptom patterns” (National Institute for Health and Clinical Excellence, 2005).