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Management and long-term complications of pediatric cancer.

The impact of recently intensified and novel therapies for the treatment of childhood cancer has been an increased number of survivors and an increase in the number of treatment complications among survivors. Thus, it is important for the primary care practitioner to be aware of not only acute but chronic complications of therapy, including the possibility of second malignancies. Long-term follow-up is essential, and continuous education of patients and health care personnel is an important aspect for the complete success of treatment. Primary care practitioners also need to incorporate other subspecialties in the management of these patients to ensure that they receive complete evaluation and treatment.

Aftercare↗

Parental decision making in pediatric cancer end-of-life care: using focus group methodology as a prephase to seek participant design input.

The ultimate aim of our research program is to provide strategies that facilitate parental decision-making for parents of children with cancer receiving end-of-life care. As a first step to develop this program, we needed insight into parents' reactions and opinions about the research methods planned for a larger study. In particular, we needed their opinions about the general experience of making the decision between palliative cytotoxic chemotherapy and supportive care alone and the factors that parents regard as important when making this decision. In addition, we wished to know whether the methodology proposed for the future study was easy to understand and whether it might cause unnecessary emotional trauma. Finally, we asked their opinions regarding the appropriate target sample of parents to include in the future study. Qualitative data about these issues were collected using focus group methodology involving seven participants. The comments made during the focus group discussions were content-analyzed for common themes. The results from the focus group discussion led to particular modifications in the proposed design and interview strategies planned for the future larger study. We found it was extremely beneficial to include a focus group pre-phase in a study that will interview parents in a high sensitivity area.

Adaptation, Psychological↗

A study of the nutritional status of pediatric cancer patients.

The records of 455 children were reviewed to investigate the relationship of nutritional status at time of first referral to various measurements of disease and survival. Initial symptoms of weight loss, anorexia, fatigue, and early satiety were all directly correlated. Serum albumin level and nutritional status were not directly correlated. Likewise, there was no direct relationship between performance status and nutritional status. However, higher values of serum albumin were associated with better performance status. Nutritional status was directly related to freedom from relapse among children with solid tumors whether they had localized or non-localized disease. In addition, improved survival was related to good nutritional status for children with localized disease, whereas those with advanced disease had a poorer survival regardless of their nutritional status. Nutritional status appears to have prognostic implications among children with cancer.

Body Height↗

Geographic and environmental factors in pediatric cancer.

It is important to determine the relative contributions of genetic and environmental factors to the etiology of childhood cancer in order to elucidate the pathogenic mechanisms involved and to develop effective means of primary prevention. Geographic differences in cancer incidence as well as changes in incidence over calendar time have long been used to generate clues to possible etiologic agents. The important role of genetic factors in childhood cancer is clear, and is exemplified by the observations in retinoblastoma. The importance of the contributions of environmental factors in general and of specific factors in particular, to the etiology of cancers in children, has proven more difficult to determine. A variety of environmental factors have been implicated to varying degrees in the etiology of different childhood cancers. These factors include physical agents such as radiation, chemical agents such as nitrosamines, and organic solvents, and infectious agents such as the Epstein-Barr virus. The observations that certain compounds may act as teratogens when a prenatal exposure occurs early in pregnancy and as carcinogens when the exposure occurs late in pregnancy, suggests that there may be a continuum of teratogenesis and carcinogenesis. This finding has major implications for the possible biologic mechanisms that could be involved in childhood cancers and for the design of future research of their etiology and prevention. The etiology of childhood cancer should be viewed as an interaction of environmental factors to which the child or his parent were exposed together with varying degrees of genetically determined susceptibility of the child to the carcinogenic effects of these factors.

Child↗

Association of psychological vulnerability factors to post-traumatic stress symptomatology in mothers of pediatric cancer survivors.

The current study investigated whether individual differences in coping style, lifetime experience of traumatic events, perceived social support, and perceived social constraints were associated with symptoms of post-traumatic stress among 72 mothers of children who had successfully completed cancer treatment. Results suggested that more perceived social constraints and less perceived belonging support were associated with significantly more post-traumatic stress symptomatology, and this association was present after controlling for the effects of child age. Monitoring coping style and lifetime traumatic events were not significantly predictive of post-traumatic stress symptoms. The results of this study indicate that a sense of belonging to a social network as well as comfort expressing cancer-related thoughts and feelings to friends and family may play a key role in mothers' long-term adjustment to this extremely difficult life experience.

Adaptation, Psychological↗

Utility of automated counting to determine absolute neutrophil counts and absolute phagocyte counts for pediatric cancer treatment protocols.

BACKGROUND: Absolute neutrophil counts (ANCs) and absolute phagocyte counts (APCs) are used to guide cancer treatment. Although automated counting could replace manual counting, data showing correlations are lacking. By analyzing blood samples from children undergoing cancer treatment, the authors determined whether ANCs and APCs obtained by automated methods correlated positively with ANCs and APCs obtained manually. METHODS: The authors analyzed 3640 consecutive peripheral blood samples. Leukocyte counts determined by Beckman-Coulter Gen-S or HmX analyzers (Beckman-Coulter, Miami, FL) were used to calculate counts obtained by automated or manual methods. Automated differential counts were obtained by automated analyzers and manual differential counts were performed by medical technologists. Counts underwent linear regression analysis. The authors evaluated 5 cutoff values for ANCs and APCs commonly used in decision-making related to cancer treatment: 300/muL, 500/muL, 750/muL, 1000/muL, and 1500/muL. Manually determined ANCs and APCs served as standards to determine the sensitivity, specificity, positive and negative predictive values, and kappa coefficient for automated counting. RESULTS: R(2) values were 0.81 for ANCs determined by manual and automated methods and 0.84 for APCs determined by both methods. The specificity of the automated method was > 90% for all ranges of ANCs and APCs, except one (APCs < 300/muL). There was excellent agreement (kappa > 0.9) between ANCs determined by manual and automated methods and APCs calculated by both methods. CONCLUSIONS: Automated methods of determining ANCs and APCs for children undergoing cancer treatment were reliable and can replace manual counting. Blood smear examination to validate ANCs and APCs determined by automated methods was needed only in selected cases.

Antineoplastic Combined Chemotherapy Protocols↗

Somatic mutant frequency at the HPRT locus in children associated with a pediatric cancer cluster linked to exposure to two superfund sites.

The somatic mutant frequency (Mf) of the hypoxanthine phosphoribosyl transferase (HPRT) gene has been widely used as a biomarker for the genotoxic effects of exposure but few studies have found an association with environmental exposures. We measured background Mfs in 49 current and former residents of Dover Township, New Jersey, who were exposed during childhood to industrially contaminated drinking water. The exposed subjects were the siblings of children who developed cancer after residing in Dover Township, where the incidence of childhood cancer has been elevated since 1979. Mfs from this exposed group were compared to Mfs in 43 age-matched, presumably unexposed residents of neighboring communities with no known water contamination and no increased cancer incidence. Statistical comparisons were based on the natural logarithm of Mf (lnMF). The mean Mf for the exposed group did not differ significantly from the unexposed group (3.90 x 10(-6) vs. 5.06 x 10(-6); P = 0.135), but unselected cloning efficiencies were higher in the exposed group (0.55 vs. 0.45; P = 0.005). After adjustment for cloning efficiency, lnMf values were very similar in both groups and age-related increases were comparable to those previously observed in healthy children. The results suggest that HPRT Mf may not be a sensitive biomarker for the genotoxic effects of environmental exposures in children, particularly when substantial time has elapsed since exposure.

Adolescent↗

Long-term follow-up of pediatric cancer survivors: education, surveillance, and screening.

Cancer and its treatment predispose childhood cancer survivors to chronic or late occurring health problems that may not become clinically significant until many years after therapy. Frequently, long-term survivors of childhood cancer report late cancer-related effects that diminish quality of life and increase the risk of early mortality. Risk-based health care that involves a personalized plan for surveillance, screening, and prevention is recommended to reduce cancer-related morbidity in childhood cancer survivors. To implement optimal risk-based care, the survivor and health care provider must have accurate information about cancer diagnosis, treatment modalities, and potential cancer-related health risks to guide screening and risk-reducing interventions. However, previous studies evaluating health knowledge of childhood cancer survivors demonstrate noteworthy deficits and misperceptions about their cancer diagnosis, treatment, and cancer-related health risks. In addition, because of the relative rarity of childhood cancer, many health care providers lack familiarity with cancer-related health risks and risk-reduction methods relevant for this population. To correct these deficits, the Scottish Intercollegiate Guidelines Network (SIGN) and the Children's Oncology Group (COG) developed clinical practice guidelines to foster appropriate risk-based survivor care. Herein, we discuss the development, benefits, and limitations of the SIGN and COG guidelines and the foundation they provide for standardizing long-term follow-up care of the ever-growing vulnerable population of childhood cancer survivors.

Adolescent↗

Validation of the oral mucositis assessment scale in pediatric cancer.

BACKGROUND: Our objective was to examine the construct validity of the Oral Mucositis Assessment Scale (OMAS) in children receiving doxorubicin chemotherapy. METHODS: Children between 6 and 18 years of age with cancer receiving doxorubicin-containing chemotherapy were included. OMAS was measured on days 7, 10, 14, and 17 after chemotherapy. Other measures of mucositis obtained concurrent with OMAS were the World Health Organization (WHO) mucositis scale and pain visual analogue scale (VAS). We also recorded analgesia administration. RESULTS: Sixteen children were studied for 45 post-chemotherapy cycles and 156 OMAS assessments were performed. OMAS was moderately correlated with WHO scores (r = 0.56; P = 0.0006) whereas correlation with the pain VAS was fair (r = 0.37; P = 0.002). OMAS also had fair correlation with the number of doses of topical analgesia (r = 0.43; P = 0.001) and with the cumulative dose of opioid analgesia (r = 0.38; P = 0.003). CONCLUSIONS: The OMAS is valid for use in mucositis clinical trials for children at least 6 years of age.

Administration, Oral↗

Intensity of CNS treatment for pediatric cancer: prediction of social outcomes in survivors.

PURPOSE: To evaluate the association of central nervous system (CNS) treatment intensity and the social functioning of children who have completed treatment for leukemia, lymphoma, and solid tumors outside the CNS. Furthermore, we expected that these associations would be moderated by child age at diagnosis and gender. METHOD: Peer, teacher, and self-report data were obtained for 82 cancer survivors (age 9-17 years) using classroom rating and nomination procedures that are widely used in research on social development. Information regarding cranial radiation therapy (CRT), intrathecal chemotherapy (ITC), and systemic methotrexate were obtained from medical records and used to create a composite index of CNS treatment intensity. RESULTS: Higher scores on the index of CNS treatment intensity were associated with poorer peer acceptance, fewer friendships, greater social sensitivity-isolation, and diminished leadership-popularity based on peer-report. These associations were stronger for boys and children who were younger (<10 years old) at diagnosis. In contrast, CNS treatment intensity was only predictive of teacher-perceptions of aggressive-disruptive behavior and it was unrelated to social self-perceptions. CONCLUSION: These results suggest that children who receive CRT and ITC are at risk for problematic peer relations, particularly if they are male or younger at diagnosis. Given the stability of poor peer relationships and documented linkages between peer problems and subsequent academic and psychiatric difficulties, clinical services should address these issues. Research is needed to identify mechanisms that account for these outcomes and provide direction for prevention and treatment efforts.

Adolescent↗

Anesthesia considerations for pediatric cancer.

The multidisciplinary approach to the care of children with cancer demands an understanding of all aspects of its treatment. Recognition of potential anatomic and physiologic derangements which may result from specific types of malignancy allows optimal preoperative preparation. Understanding the anesthetic implications of cancer chemotherapy, irradiation and surgery, and the medical complications which result, is essential. The anesthesiologist is involved in critical perioperative issues during surgical resection in the operating room, but just as importantly plays a crucial role in a variety of procedures performed in remote locations. An awareness of special problems related to cancer and its treatment allows optimal anesthesia care while dealing with such issues as radical surgery, organ system failure, acute and chronic pain, and terminal illness.

Abdominal Neoplasms↗

Cerebellar sclerosis in pediatric cancer patients.

Cerebral cortical sclerosis is an acquired condition that has rarely been described in cancer patients. We reviewed necropsy findings in all children with cancer who died at the Children's Hospital of Philadelphia during the 20 year period 1963-1982 and found cerebellar sclerosis in 14 children with cancer (12 with acute lymphoblastic leukemia, 1 each with neuroblastoma and osteogenic sarcoma). The lesions were focal (3), multifocal (9) or diffuse (2). They occurred more frequently in children with acute lymphoblastic leukemia who had received intravenous methotrexate therapy. Ten of these 12 children had also received whole brain irradiation. The pathogenesis of the cerebellar sclerosis is unknown, but it is possible that extrinsic cerebellar compression by tumor or chronically increased intracranial pressure may have played a role in 6, ischemia/hypoxia in 3, and methotrexate toxicity in 2. No clear associations could be ascertained in 3. Methotrexate may be a previously unrecognized cause of cerebellar cortical injury. In addition, oncologic treatment regimens that include other central nervous system-penetrating drugs and irradiation may sensitize cerebellar cortex and make it more susceptible to other cerebellar sclerosis-causative factors.

Cerebellum↗

Evaluation of a novel bis-naphthalimide anticancer agent, DMP 840, against human xenografts derived from adult, juvenile, and pediatric cancers.

The new bis-naphthalimide antitumor agent (R,R)2,2'-[1,2-ethanediylbis[imino(1-methyl-2.1-ethanediyl)]-bis(5 -nitro 1H-benz[de]-isoquinoline-1,3-2H) dione] dimethanesulfonate (DMP 840) was evaluated against parental and multidrug-resistant human KB cell lines in vitro and against these lines growing as xenografts in immune-deprived mice. In vitro, KB8-5 cells were 50-fold resistant to vincristine but only 16-fold resistant to DMP 840 as measured by clonogenic survival. For in vivo evaluation, DMP 840 was given by i.v. injection daily for 9 days or for 5 days/week for 2 consecutive weeks [(dx5)2]. In contrast to the cross-resistance of KB cell lines in vitro, both KB3-1 and KB8-5 tumors were highly and equally sensitive to DMP 840; only KB3-1 xenografts demonstrated sensitivity to vincristine, which was consistent with the in vitro results. DMP 840 was also evaluated against a panel of human tumors comprising colon adenocarcinoma and rhabdomyosarcoma xenografts. Against eight lines of colon adenocarcinoma, DMP 840 caused a high frequency of partial and complete regressions in two lines and significant inhibition of growth in two lines. DMP 840 caused complete regressions in five of six lines of advanced rhabdomyosarcomas, demonstrating a broad range of effective dose levels. The pattern of activity against this tumor panel was similar but not identical to that of two inhibitors of topoisomerase I. There was no cross-resistance to DMP 840 in xenografts selected for resistance to vincristine or in a rhabdomyosarcoma selected for resistance to the topoisomerase I inhibitor topotecan. In contrast, a colon tumor selected for topotecan resistance was completely resistant to DMP 840. Slight cross-resistance to DMP 840 was demonstrated in a rhabdomyosarcoma xenograft that was selected for primary resistance to melphalan and was cross-resistant to topoisomerase I inhibitors. The pattern of activity and cross-resistance in these tumors was compared with that shown by two agents that inhibit topoisomerase I: topotecan and CPT-11.

Adenocarcinoma↗