Fertility preservation medicine: A new field in the care of young cancer survivors

Treatment modalities for numerous oncological and non‐oncological conditions result in gonadal insufficiency and infertility. Furthermore, pelvic‐abdominal radiation may result in uterine damage resulting in poor reproductive outcomes such as preterm birth, low birth weight, and spontaneous abortion in adult survivors of childhood cancers. In response to the recognition of the impact of cancer treatments on fertility, several fertility preservation techniques have been developed. In prepubertal children, fertility preservation options are usually limited to ovarian cryopreservation because of sexual immaturity, but oocyte freezing can be performed in adolescent children. Two prospective randomized studies showed no benefit of gonadal suppression with GnRH analogs to preserve gonadal function and thus this treatment should not be recommended. For adult survivors of childhood cancer who experienced reproductive failure, third party reproduction techniques are highly successful. Pediatr Blood Cancer 2009;53:267–273. © 2009 Wiley‐Liss, Inc.     

A questionnaire based review of long-term follow-up programs for survivors of childhood cancer in Canada

Background

Major advances have been made in the treatment of childhood cancer; however, survivors of childhood cancer are at increased risk for morbidity and mortality. There is little literature regarding available long‐term follow‐up programs for survivors of childhood cancer.

Procedure

In March 2007, 16 surveys were sent to pediatric hematology/oncology programs across Canada to determine what programs were available for survivors of childhood cancer, and the nature of such programs.

Results

Of 15 participating centers, 13 (87%) have multi‐disciplinary programs for the long‐term follow‐up of pediatric cancer survivors. Research databases were documented in 9/15 (60%) of centers to document late effects. Dedicated programs for adult survivors of childhood cancer were established in 8/15 (53%) of centers. Access to subspecialty care for survivors was rated as quite good. Concerns were raised by many participants about patients being lost to follow‐up. Respondents indicated that primary care physicians appear to be under‐represented within dedicated long‐term follow‐up programs.

Conclusion

Long‐term follow‐up programs for survivors of childhood cancer are available in 87% of Canadian pediatric oncology centers. While programs reported good access to care for childhood survivors, many adult survivors of childhood cancer have more limited timely access to services and patients are often lost to follow‐up. New models of care incorporating primary care physicians are necessary due to growing numbers of survivors. Pediatr Blood Cancer 2009;52:113–115. © 2008 Wiley‐Liss, Inc.     

Children’s exposure to diagnostic medical radiation and cancer risk: epidemiologic and dosimetric considerations

While the etiology of most childhood cancers is largely unknown, epidemiologic studies have consistently found an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The relation between early life diagnostic radiation exposure and occurrence of pediatric cancer risks is less clear. This review summarizes current and historical estimated doses for common diagnostic radiologic procedures as well as the epidemiologic literature on the role of maternal prenatal, children’s postnatal and parental preconception diagnostic radiologic procedures on subsequent risk of childhood malignancies. Risk estimates are presented according to factors such as the year of birth of the child, trimester and medical indication for the procedure, and the number of films taken. The paper also discusses limitations of the methods employed in epidemiologic studies to assess pediatric cancer risks, the effects on clinical practice of the results reported from the epidemiologic studies, and clinical and public health policy implications of the findings. Gaps in understanding and additional research needs are identified. Important research priorities include nationwide surveys to estimate fetal and childhood radiation doses from common diagnostic procedures, and epidemiologic studies to quantify pediatric and lifetime cancer risks from prenatal and early childhood exposures to diagnostic radiography, CT, and fluoroscopically guided procedures.     

Children's Oncology Group's 2013 blueprint for research: Survivorship and outcomes

Improvements in the treatment of childhood cancer have resulted in over 360,000 survivors of childhood cancer in the U.S. There is now a heightened recognition of the need to reduce treatment‐related sequelae and optimize the quality of life of children treated for cancer. Survivorship studies conducted in the cooperative group setting have provided us with important information on long‐term intellectual function, organ toxicity, reproductive outcomes, second cancers, late mortality, and disparities in outcomes. Ongoing health education initiatives have helped standardize the follow‐up care for childhood cancer survivors and facilitate the early transfer of health‐related information to patients, families, and healthcare providers. Pediatr Blood Cancer 2013; 60: 1063–1068. © 2012 Wiley Periodicals, Inc.     

Transgenerational tobacco smoke exposure and childhood cancer: An observational study

Aim: Although tobacco smoke is an established risk factor for adult cancer, studies of the association between parental smoking and childhood cancer have produced inconsistent results. To investigate the transgenerational relationship between pre‐natal and post‐natal tobacco smoke exposure from the grandmother's pregnancies until after the post‐natal period and childhood cancer. Methods: Exposure to tobacco smoke was recorded for three generations. Data were collected through personal interviews using the paediatric environmental history, and were compared among 128 children with cancer and 128 matched controls. The contingency tables and a logistic multivariable regression model were used to control for possible confounding factors. Results: Smoke exposure during oogenesis (maternal grandmother smokers) – odds ratio (OR) 2.2 (95% confidence interval (CI) 1.1–4.9) – and during the mother’ pregnancies – OR 1.8 (95% CI 1.1–3.3) – were significantly associated with an increased risk of childhood cancer. Conclusions: Tobacco smoke exposure during the grandmother's and mother's pregnancies increase the risk of cancer in the descendants. The results suggest that the biological plausibility of the association between parental smoking and paediatric cancer can be explained by the large latency period of paediatric carcinogenesis.     

Influence of outdoor NO2 exposure on asthma in childhood: Meta‐analysis

Background: It has long been assumed that the development of childhood asthma is related to exposure to environmental chemicals, but it has thus far not been possible to unequivocally establish this suspected relationship using individual studies. Moreover, studies of children have been scanty and unreliable due to the large diversity of research environments and subject cohorts. The aim of the current study was to clarify this relationship for one factor by means of a meta‐analysis of studies investigating the influence of NO₂ exposure on symptomatology of childhood asthma. Methods: Two electronic databases ( MEDLINE and EMBASE ) were searched for literature on relationships between environmental chemical exposure and development of childhood asthma using the MeSH terms ‘nitrogen dioxide’ and ‘asthma’. This was done according to the MOOSE guidelines for meta‐analyses of observational studies. Results: A total of 130 papers were retrieved, of which 12 met the selection criteria. These papers described observational studies from seven countries. Study subjects were 97 932 ordinary children aged 0–18 years. Using random model analysis, the odds ratio (OR) for asthma development due to an increment of 10 p.p.b. NO₂ was 1.135 with a 95% confidence interval [CI] of 1.031–1.251 (P= 0.01), while the OR for wheezing symptoms was 1.052 with a 95%CI of 1.020–1.085 (P= 0.001). It is therefore evident that NO₂ exposure does influence the development of asthma in ordinary children. Conclusions: Exposure to NO₂ in the air significantly influences the development of childhood asthma and symptoms of wheezing.     

Trends in the incidence of childhood and adolescent cancer in connecticut, 1935–1979

Trends in the incidence of childhood cancer in Connecticut are reported and analyzed for the period 1935-1979 by 5-year age groups (0–4, 5–9, 10–14, 15–19 years), using a log linear model method. A threefold increase (P < .001) in the incidence of ALL in males 0–4 years of age was observed, with significant increases of smaller magnitude seen in males aged 5–9 and 15–19 and females aged 0–4 and 5–9. The incidence of central nervous system cancers also increased in several age groups for both sexes with the largest increase seen in males 0–4 years old. Significant increases in incidence of large magnitude were also observed for Hodgkin's disease, in males aged 15–19 years and females aged 10–19 years, for neuroblastoma in both sexes at ages 0–4 years, and for testis and ovarian cancer at ages 15–19 years. This study of trends in incidence of childhood cancers by 5-year age groups has revealed significant changes, which would not have been as apparent if broader age groups had been used. These results provide relevant data for investigating the etiology of cancer during infancy, childhood, and adolescence. Trends in Connecticut are compared with findings from other registries in the United States and other countries.     

U.S. childhood cancer survival, 1973–1987

The surveillance, epidemiology, and end-results (SEER) data on 5-year relative survival rates (1973-1987) for the most common pediatric tumors (ages 0–14) were analyzed. The SEER data are population based, so the observed progress in survival from childhood cancer represents the real impact that development in cancer treatment had on the population followed by the registry. The greatest increase in survival rate from 1973 until 1987 has been achieved in hematopoietic tumors such as acute lymphocytic leukemia (ALL), in which survival increased from 47.6% (1973–1977) to 60.8% (1983–1987), and Burkitt's lymphoma in which survival increased from 27.6% (1973–1977) to 68.7% (1983–1987). Solid tumors showed a less steep, but steady increase in survival rates. Flattening in the survival rates since 1978–1982 has been observed for acute leukemia, astrocytoma, medulloblastoma, and osteosarcoma. Females have better survival rates for most pediatric tumors, except Hodgkin's disease. Analysis of race of childhood leukemia confirmed that black children have worse survival than white. When solid tumors were analyzed by stage at presentation, there was no indication that diagnosis in earlier stages of disease accounted for the improved survival. Observed flattening in the survival rates since 1978–1982 of leukemia and some solid tumors warrants further follow-up. © 1994 Wiley-Liss, Inc.     

Specific Deficit Analyses in Motor Performance and Quality of Life of Pediatric Cancer Patients—A Cross-Sectional Pilot Study

Although survival rates in childhood cancer have distinctly improved, pediatric cancer patients often experience various disease- and treatment-related side effects with long-term consequences. Despite current studies investigating inactivity and limitations in physical functioning and quality of life in pediatric cancer patients, only little information regarding specific deficits in physical functioning and quality of life has been available until now. No study has yet analyzed these parameters from a global perspective and then identified specific deficits in a mixed childhood cancer population. Within this cross-sectional pilot study, motor performance and quality of life of 26 pediatric cancer patients were assessed after inpatient medical treatment, using standardized motor test batteries (MOT 4–6; DMT 6–18) and a quality of life questionnaire (KINDL®). Reference data have been mainly provided by the German “Children and Young People Health Survey” (KiGGS). Patients achieved lower motor performance scores (p = .000) (more than 27% below the average of healthy peers). Specific deficits were identified in motor speed and motor control (4–6 years), as well as in endurance, strength and coordination under time pressure (6–17 years). In terms of quality of life, no significant differences were examined compared to healthy children of the same age. The results of this study confirm that children with oncological diseases frequently have specific motor problems. Future research in pediatric oncology must investigate the impact of targeted, individualized exercise interventions addressing these specific deficits.     

儿童恶性肿瘤幸存者健康相关生活质量研究进展

随着医疗科学技术的发展,儿童恶性肿瘤的幸存者越来越多,幸存者的健康相关生活质量(HRQoL)逐渐成为关注的焦点。儿童恶性肿瘤幸存者除了要承受疾病带来的生理、心理、社会的压力,还将要面对由治疗带来的生长发育障碍、性腺功能障碍及癌症远期效应,如脏器功能损害和二次肿瘤。大量研究显示,恶性肿瘤HRQoL显著低于健康人群,但也有少量的研究认为癌症经历对幸存者的生活质量可能有积极的影响。目前HRQoL的评价主要通过生活质量量表完成,后者可以从躯体健康、心理健康、社会健康和精神健康等方面进行综合评价。期待更多的观察性、横断面、尤其是长期随访研究来进一步描述儿童恶性肿瘤幸存者的HRQoL,这样可以为更多的干预研究提供基础,更为临床工作者的临床决策提供循证依据。     

Radiation and breast carcinogenesis*

With the possible exception of radiation‐induced leukemia, more is known about radiation‐induced breast cancer than any other malignancy [ 1 , 2 ]. Fourteen cohort studies have provided quantitative information on the level of risk following a wide range of doses in different populations around the world. Comprehensive studies have been conducted in Canada, Germany, Japan, Sweden and other Nordic countries, the United Kingdom, and the USA (Table I). Key features are the linearity in the dose response (i.e., a straight line adequately fits the observed data), and the effect modification of age at exposure (i.e., risk is inversely related to exposure age and exposures past the menopausal ages appear to carry a very low risk); and the minimal effect of fractionating dose on subsequent risk [ 3 ]. A recent combined analysis of almost 78,000 women and 1,500 breast cancer cases from eight cohorts confirmed the downturn in risk at the highest dose levels (related in part to the killing of cells rather than transformation) and that fractionation of dose has little influence on risk, at least on an absolute scale [ 4 ]. It is not known whether persons predisposed to cancer are at enhanced risk of radiation‐induced breast cancer from low‐dose exposures, although this seems unlikely [ 5 ]. New data on the effects of high doses following childhood exposures will be forthcoming from long‐term studies of the survivors of childhood cancer ( 6 - 8 ). Med. Pediatr. Oncol. 36:508–513, 2001. © 2001 Wiley‐Liss, Inc.     

Cancer risks following diagnostic and therapeutic radiation exposure in children

The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life.     

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.     

Epidemiology of childhood acute myeloid leukemia

Although leukemia is the most common childhood cancer diagnosis, the subtype, acute myeloid leukemia (AML), is less common and fewer etiologic studies exist. This review summarizes the major risk factors for AML. We searched the literature using PubMed for articles on childhood AML and reviewed 180 articles. While few risk factors are definitive, we identified several with consistent evidence of a possible effect. Thorough analysis of genetic and epigenetic factors is missing from this literature and methodological issues are unresolved. Future studies should more closely examine causal mechanisms, improve exposure measurement, and include analysis using genetic and epigenetic factors. Pediatr Blood Cancer 2013; 60: 728–733. © 2013 Wiley Periodicals, Inc.     

Management of the obese child using psychological-based treatments

Obesity is increasing in childhood and has approximately doubled during the last 10 years. Nowadays, more politicians and researchers find it necessary to start treating childhood obesity. The reasons for this are the high costs of obesity and its complications later in life—complications that also appear when obesity starts in childhood. In the following article, I will give a review of the treatments available that have been evaluated in studies. There are no relevant studies regarding surgery and medication in children. Thus, I will not comment further on those treatments. The treatment of choice is thus a change in lifestyle. To be able to help patients do this, you have to be professional when you encounter the patient. The best way to be successful is to use psychological treatments as described in this paper.     

Papillary thyroid cancer presenting as Horner syndrome

Thyroid carcinomas are an uncommon entity in childhood. We report a case of papillary thyroid cancer presenting as Horner syndrome in a 14 year‐old child, which is the only reported such case in the pediatric population. Pediatr Blood Cancer. 2010;55:739–741. © 2010 Wiley‐Liss, Inc.     

Health-related behaviors of survivors of childhood cancer

The health-related beliefs and behaviors of long-term survivors of childhood cancer are important because of vulnerability to adverse late effects from their primary malignancy and its therapy. A health behavior survey was completed by 110 parents of long-term survivors ranging in age from 11–17 years, and by 40 adult long-term survivors of childhood cancer ranging in age from 18–29 years. The survey included questions on the former patient's frequency of alcohol and tobacco use, as well as diet, exercise, sleep, dental, and seatbelt habits. The reported prevalence of tobacco and alcohol use was less than 10% among those less than 18 years old. Among the adults, tobacco (17.5%) and alcohol (72.5%) use was greater, but problem drinking was infrequently reported. In order to assess their perceived vulnerability, we asked the parents and the young adult patients to rate the strength of their belief that it is more important for the patient to keep healthy compared to most other children or young adults. Contrary to our expectations, demographic factors such as the patient's gender, socioeconomic level, or time elapsed since completion of therapy exerted minimal influence on their responses. Over 80% of parents and 60% of young adult survivos believed that it was more important for the former patient to remain healthy compared to most other people. However, this shared belief in increased vulnerability was inconsistently expressed in the patient's health behaviors. These results suggest that specific changes are needed in the health assessment and education of long-term survivors of childhood cancer. © 1995 Wiley-Liss, Inc.     

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.     

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.     

Molecular epidemiology study of a suspected community cluster of childhood cancers

We investigated the report of a community cluster of cancers in 33 children, which included two siblings known to have dominantly inherited Li-Fraumeni syndrome and a germline p53 mutation. After defining criteria for inclusion in the cluster, the 12 eligible childhood cancer probands diagnosed between 1980 and 1989 were not excessive (expected, ten cases). The corresponding childhood cancer mortality rates for the community fluctuated between 1950 and 1989 and were not increased overall. However, three additional probands had family histories of childhood cancer that suggested a forme fruste of Li-Fraumeni syndrome. The epidemiological data suggested a geographic cluster of this rare hereditary disorder, but absence of germline p53 mutation in the three other multicase families indicates genetic heterogeneity. Laboratory studies can assist analyses of suspected clusters, although investigations of geographic clusters of hereditary cancers raise complex issues of confidentiality and protection of affected individuals, their families, and the community. Med. Pediatr. Oncol. 28:243–247. © 1997 Wiley-Liss, Inc.