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Hopefulness in adolescents with cancer serves critical functions related to the adolescents' sense of well-being and commitment to treatment. Given these critical functions, it is important to determine the essential characteristics of hopefulness, which include the degree and dynamism of hopefulness and the nature and attributes of hoped-for objects. The purposes of this two-site study were to describe the degree and dynamism of hopefulness at four time points during the first 6 months of adolescents' treatment for newly diagnosed cancer to identify and describe the adolescents' hoped-for objects, and to evaluate potential relationships between the characteristics of hopefulness and patient gender age, diagnosis, and time point in treatment. Seventy-eight adolescents completed the Hopefulness Scale for Adolescents, the Hopelessness Scale, and the Hopefulness Interview Question at each time point. Hopefulness scores were higher and hopelessness scores substantially lower than reported in other tested samples. Adolescents identified a total of 57 different hopes. Differences by age, gender and diagnosis were found. [ABSTRACT FROM AUTHOR]

We surveyed 65 patients age 13 years or older who had been treated for malignant bone tumors and were in remission at least 1 year after limb-sparing surgery (LS) or amputation (AMP) to assess general satisfaction with the surgical outcome and its impact on various areas of functioning. Of 130 eligible patients, 65 responded (61 treated for osteosarcoma, 3 for Ewing's sarcoma, and 1 for mesenchymoma). The median current age of the cohort was 25.8 years (range, 14.2 to 47.5 years). The median time from surgery was 14.2 years (range, 4.0 to 30.4 years) for the AMP group, and 5.5 years (range, 2.0 to 13.8 years) for the LS patients. Questionnaire responses of patients treated with AMP compared to those who had LS surgery showed no significant differences in the impact of the surgical procedure on educational and occupational status, functional limitations, pain intensity and degree of pain interference, emotional distress, interpersonal/social interactions and self-image, rehabilitation experience, and overall satisfaction with the surgical procedure. Functional limitation was significantly related to pain interference, as well as emotional distress, self-image, and interpersonal difficulties for the entire cohort. Our findings highlight procedure-related advantages and difficulties that may potentially enhance decision making regarding the selection of the surgical procedure for individual patients with malignant bone tumors of an extremity. Copyright (c) 1998 by Association of Pediatric Oncology Nurses [ABSTRACT FROM AUTHOR]

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Advances in the development of chimeric antigen receptor (CAR)-T cells have undermined the paramount importance of this technology for the success of adoptive T-cell immunotherapy. The bespoke production of autologous CAR-T cells is a lengthy and costly process. Thus, the development of more cost-effective allogeneic 'off-the-shelf' CAR-T cells provides a more readily available treatment option. The exploration of methods to reduce costs and to determine which CAR-T cells are the most effective is key for providing this breakthrough treatment to most patients. The process from the design and development of CAR-T cells, through pre-clinical and clinical testing and manufacturing, to patient monitoring involves a variety of high-throughput tools that enable the monitoring of all processes to ensure the safety and efficacy of the treatment., (Copyright © 2022. Published by Elsevier Ltd.)

Recent reports of haemagglutinin antigen (HA) mismatch between vaccine composition strains and circulating strains, have led to renewed interest in influenza B viruses. Additionally, there are concerns about resistance to neuraminidase inhibitors in new influenza B isolates. To assess the potential impact in Ghana, we characterized the lineages of influenza B viruses that circulated in Ghana between 2016 and 2017 from different regions of the country: Southern, Northern and Central Ghana. Eight representative specimens from the three regions that were positive for influenza B virus by real-time RT-PCR were sequenced and compared to reference genomes from each lineage. A total of eleven amino acids substitutions were detected in the B/Victoria lineage and six in the B/Yamagata lineage. The strains of influenza B viruses were closely related to influenza B/Brisbane/60/2008 and influenza B/Phuket/3073/2013 for the Victoria and Yamagata lineages, respectively. Three main amino acid substitutions (P31S, I117V and R151K) were found in B/Victoria lineages circulating between 2016 and 2017, while one strain of B/Victoria possessed a unique glycosylation site at amino acid position 51 in the HA2 subunit. Two main substitutions (L172Q and M251V) were detected in the HA gene of the B/Yamagata lineage. The U.S. CDC recently reported a deletion sub-group in influenza B virus, but this was not identified among the Ghanaian specimens. Close monitoring of the patterns of influenza B evolution is necessary for the efficient selection of representative viruses for the design and formulation of effective influenza vaccines., Competing Interests: The authors have declared that no competing interests exist.

Knowledge of contemporary genetic composition of dengue virus (DENV) in Africa is lacking. By using next-generation sequencing of samples from the 2017 DENV outbreak in Burkina Faso, we isolated 29 DENV genomes (5 serotype 1, 16 serotype 2 [DENV-2], and 8 serotype 3). Phylogenetic analysis demonstrated the endemic nature of DENV-2 in Burkina Faso. We noted discordant diagnostic results, probably related to genetic divergence between these genomes and the Trioplex PCR. Forward and reverse1 primers had a single mismatch when mapped to the DENV-2 genomes, probably explaining the insensitivity of the molecular test. Although we observed considerable homogeneity between the Dengvaxia and TetraVax-DV-TV003 vaccine strains as well as B cell epitopes compared with these genomes, we noted unique divergence. Continual surveillance of dengue virus in Africa is needed to clarify the ongoing novel evolutionary dynamics of circulating virus populations and support the development of effective diagnostic, therapeutic, and preventive countermeasures.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objective: Public trust in physicians and public health literacy (HL) are important factors that ensure the effectiveness of health-care delivery, particularly that provided during the SARS-CoV-2 pandemic. This study investigates HL as a predictor of public trust in physicians in China's ongoing efforts to control COVID-19. Methods: Data were gathered in February 2020 during the peak of the disease in China. Based on Nutbeam's conceptualization of HL, we measure HL vis-à-vis COVID-19 by using a six-item scale that includes two items each for functional, interactive, and critical HL. Trust in physicians was measured by assessing physicians' capability to diagnose COVID-19. A rank-sum test and ordinal logit regression modeling were used to analyze the data. Results: Two key findings: (a) trust in physician handling of treatment for COVID-19 is reported by about 74% of respondents; and (b) five of the six HL measures are positive predictors of public trust in physician treatment of the disease, with functional HL1 having the highest level of such association (coefficient 0.285, odds ratio 1.33%, p < 0.01). Conclusions: Improving public HL is important for better public-physician relationships, as well as for nations' efforts to contain the pandemic, serving as a possible behavioral, non-clinical antidote to COVID-19. Being confronted with the unprecedented virus, humans need trust. Health education and risk communication can improve public compliance with physicians' requirements and build a solid foundation for collective responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Zhou, Pratt, Su and Gu.)

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.

Containing the spread of SARS-CoV-2 is a daunting challenge globally. China, as well as a handful of other countries, has, for the most part, contained it by implementing strict policies. Wuhan's citywide virus-testing program presents a way forward in preventing and controlling the uncertainty, anxiety, instability and complexity it faces over the outbreak of SARS-CoV-2. Inarguably, the health crisis requires time-tested strategies and tactics for coordinating governments' and social entities' response to the health crisis, with a goal toward having and ensuring sustained effectiveness. Because of a possible recurrence of SARS-CoV-2 in Wuhan, the Prevention and Control Headquarters of Wuhan on COVID-19 launched a massive virus testing of Wuhan's 11 million residents; it was completed within 10 days. In light of this unprecedented mass testing, this study applies the situational crisis communication theory to analyze this massive virus-testing process and the mechanisms involved to contain SARS-CoV-2 in Wuhan. While many countries still have partial lockdowns, the second outbreak in Wuhan was an indication of what awaited all SARS-CoV-2-stricken countries post-lockdowns and after community restrictions had been lifted. Therefore, the recently implemented Wuhan control mechanism (in cities, districts and townships) may become a hortatory guide to other world regions as they contend with and consider appropriate measures to control the spread of SARS-CoV-2 and to ensure public safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Seesaghur, Akhtar, Boolakee and Pratt.)

On 1 August 2018, the Democratic Republic of the Congo (DRC) declared its tenth Ebola virus disease (EVD) outbreak. To aid the epidemiologic response, the Institut National de Recherche Biomédicale (INRB) implemented an end-to-end genomic surveillance system, including sequencing, bioinformatic analysis and dissemination of genomic epidemiologic results to frontline public health workers. We report 744 new genomes sampled between 27 July 2018 and 27 April 2020 generated by this surveillance effort. Together with previously available sequence data (n = 48 genomes), these data represent almost 24% of all laboratory-confirmed Ebola virus (EBOV) infections in DRC in the period analyzed. We inferred spatiotemporal transmission dynamics from the genomic data as new sequences were generated, and disseminated the results to support epidemiologic response efforts. Here we provide an overview of how this genomic surveillance system functioned, present a full phylodynamic analysis of 792 Ebola genomes from the Nord Kivu outbreak and discuss how the genomic surveillance data informed response efforts and public health decision making.

Background: From November 2018 through February 2019, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions., Methods: Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events., Results: After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission., Conclusions: Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission. (Funded by the Ministerio de Salud y Desarrollo Social de la Nación Argentina and others.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: An alarming rise in reported Lassa fever cases continues in west Africa. Liberia has the largest reported per capita incidence of Lassa fever cases in the region, but genomic information on the circulating strains is scarce. The aim of this study was to substantially increase the available pool of data to help foster the generation of targeted diagnostics and therapeutics., Methods: Clinical serum samples collected from 17 positive Lassa fever cases originating from Liberia (16 cases) and Guinea (one case) within the past decade were processed at the Liberian Institute for Biomedical Research using a targeted-enrichment sequencing approach, producing 17 near-complete genomes. An additional 17 Lassa virus sequences (two from Guinea, seven from Liberia, four from Nigeria, and four from Sierra Leone) were generated from viral stocks at the US Centers for Disease Control and Prevention (Atlanta, GA) from samples originating from the Mano River Union (Guinea, Liberia, and Sierra Leone) region and Nigeria. Sequences were compared with existing Lassa virus genomes and published Lassa virus assays., Findings: The 23 new Liberian Lassa virus genomes grouped within two clades (IV.A and IV.B) and were genetically divergent from those circulating elsewhere in west Africa. A time-calibrated phylogeographic analysis incorporating the new genomes suggests Liberia was the entry point of Lassa virus into the Mano River Union region and estimates the introduction to have occurred between 300-350 years ago. A high level of diversity exists between the Liberian Lassa virus genomes. Nucleotide percent difference between Liberian Lassa virus genomes ranged up to 27% in the L segment and 18% in the S segment. The commonly used Lassa Josiah-MGB assay was up to 25% divergent across the target sites when aligned to the Liberian Lassa virus genomes., Interpretation: The large amount of novel genomic diversity of Lassa virus observed in the Liberian cases emphasises the need to match deployed diagnostic capabilities with locally circulating strains and underscores the importance of evaluating cross-lineage protection in the development of vaccines and therapeutics., Funding: Defense Biological Product Assurance Office of the US Department of Defense and the Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance and Response Section., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures)., Methods: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp., Findings: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name "Tumba". This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10 -3 substitutions per site per year with "Tumba" vs 1·06 × 10 -3 substitutions per site per year without "Tumba"). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail., Interpretation: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures., Funding: Defense Biological Product Assurance Office., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province., Methods: We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus., Findings: The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay., Interpretation: The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP 12 ) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures., Funding: Defense Biological Product Assurance Office., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The fimbriae of Bordetella pertussis are required for colonization of the human respiratory tract. Two serologically distinct fimbrial subunits, Fim2 and Fim3, considered important vaccine components for many years, are included in the Sanofi Pasteur 5-component acellular pertussis vaccine, and the World Health Organization recommends the inclusion of strains expressing both fimbrial serotypes in whole-cell pertussis vaccines. Each of the fimbrial major subunit genes, fim2, fim3, and fimX, has a promoter poly(C) tract upstream of its -10 box. Such monotonic DNA elements are susceptible to changes in length via slipped-strand mispairing in vitro and in vivo, which potentially causes on/off switching of genes at every cell division. Here, we have described intra-culture variability in poly(C) tract lengths and the resulting fimbrial phenotypes in 22 recent UK B. pertussis isolates. Owing to the highly plastic nature of fimbrial promoters, we used the same cultures for both genome sequencing and flow cytometry. Individual cultures of B. pertussis contained multiple fimbrial serotypes and multiple different fimbrial promoter poly(C) tract lengths, which supports earlier serological evidence that B. pertussis expresses both serotypes during infection., (© 2014 Crown copyright 2014. Reproduced with the permission of the controller of Her Majesty's Stationery Office/Queen's Printer for Scotland and Public Health England.)

Background: Natural immunity to Neisseria meningitidis may result from nasopharyngeal carriage of closely related commensals, such as Neisseria lactamica., Methods: We enrolled 61 students with no current carriage of Neisseria species and inoculated them intranasally with 10,000 colony-forming units of Neisseria lactamica or sham control. Colonization was monitored in oropharyngeal samples over 6 months. We measured specific mucosal and systemic antibody responses to N. lactamica and serum bactericidal antibody (SBA) and opsonophagocytic antibodies to a panel of N. meningitidis serogroup B strains. We also inoculated an additional cohort following vaccination with N. lactamica outer-membrane vesicles (OMV) produced from the same strain., Results: Twenty-six (63.4%) of 41 inoculated individuals became colonized with N. lactamica; 85% remained colonized at 12 weeks. Noncarriers were resistant to rechallenge, and carriers who terminated carriage were relatively resistant to rechallenge. No carriers acquired N. meningitidis carriage over 24 weeks, compared with 3 control subjects (15%). Carriers developed serum IgG and salivary IgA antibodies to the inoculated N. lactamica strain by 4 weeks; noncarriers and control subjects did not. Cross-reactive serum bactericidal antibody responses to N.meningitidis were negligible in carriers, but they developed broad opsonophagocytic antimeningococcal antibodies. OMV vaccinees developed systemic and mucosal anti-N. lactamica antibodies and were relatively resistant to N. lactamica carriage but not to natural acquisition of N. meningitidis., Conclusions: Carriers of N. lactamica develop mucosal and systemic humoral immunity to N. lactamica together with cross-reacting systemic opsonophagocytic but not bactericidal antibodies to N. meningitidis. Possession of humoral immunity to N. lactamica inhibits acquisition of N. lactamica but not of N. meningitidis. Some individuals are intrinsically resistant to N. lactamica carriage, independent of humoral immunity.

Background: Better predictors of outcome would allow improved risk-adapted therapy for pediatric nonmetastatic osteosarcoma of the extremity. We investigated the predictive value of MR imaging-based measures of absolute and relative tumor size and volume at the time of diagnosis. We also assessed the relation of tumor size to age and histologic response., Methods: We retrospectively abstracted demographic, treatment history, and outcome information of patients treated on a single institutional protocol. A single pediatric oncologic radiologist manually measured each primary lesion and the affected native bone in three dimensions on MR images obtained at the time of diagnosis. Eight parameters of tumor size were analyzed for their value in predicting overall survival (OS) and event-free survival (EFS)., Results: The median age of the 42 patients was 13.5 years (range: 5.9-18.7 years); 50% were female and 74% were Caucasian. Absolute tumor volume was an important predictor of OS (P < 0.05); absolute tumor depth (analyzed as a continuous variable) was a significant predictor of OS (P = 0.018) and EFS (P = 0.036). Relative measures of tumor size were not found to predict outcome. No relation was seen between tumor size and histologic response., Conclusions: Absolute tumor size at the time of diagnosis is significantly predictive of OS and EFS. If validated in a larger study, this indicator should be used in the design of risk-adapted treatment protocols for osteosarcoma., (2004 Wiley-Liss, Inc.)

Background: High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2., Methods: The literature was reviewed for osteosarcoma trials, use of dialysis-based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate-release trial., Results: Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade >/= 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods., Conclusions: HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently., (Copyright 2004 American Cancer Society.)

Background: Pediatric paraganglioma is rare and extraadrenal paraganglioma has not been characterized in children., Methods: The authors reviewed the medical records and pathology samples of children with extraadrenal paraganglioma treated at our institution between December 1978 and September 2000. Clinical presentation, treatment, and outcome were evaluated., Results: Eight patients (median age, 11.4 years) were identified, 4 were boys and none had a family history of paraganglioma or associated syndromes. Primary tumors arose in the retroperitoneum (n = 3), carotid body (n = 2), jugulotympanic ganglion (n = 1), cervical-paraspinal region (n = 1), and lung (n = 1). Extraadrenal paraganglioma had not been suspected at presentation in any patient. Of 5 patients who underwent gross total resection at the time of diagnosis, 4 remain disease free, 1 had microscopic residual tumor and died of disease. Three patients had initially unresectable disease, 2 are disease free after neoadjuvant therapy and delayed surgery, and 1 has persistent disease after tumor embolization and radiotherapy., Conclusions: Pediatric extraadrenal paraganglioma occurs most commonly in the retroperitoneum and head and neck, and the diagnosis usually is not suspected at the time of presentation. Surgery is the mainstay of treatment, and outcome is good after gross total resection. Neoadjuvant therapy can facilitate complete resection of initially unresectable tumors.

Stroke is a major cause of death and disability, especially among African Americans. Yet research on stroke knowledge and barriers to stroke prevention among African Americans is limited. This study used a 50-item questionnaire to conduct structured telephone interviews with 379 African American adults, 50 years or older. The questionnaire included questions on stroke knowledge, stroke risk behaviors, and barriers to stroke prevention. A stroke knowledge score was computed by assigning points for correct responses on knowledge items. The average stroke knowledge score of participants was 10.9, out of a maximum possible score of 27. Stroke knowledge was significantly related to the presence of hypertension, heart disease, diabetes, and family history of stroke. College education was significantly associated with older respondents' stroke knowledge. Younger college-educated respondents had more knowledge about the risky behaviors that lead to stroke than those with less education. Respondents preferred hospitals to churches or senior centers for receiving stroke information and for learning about stroke from their physicians. Stress and poor financial status were most frequently reported as barriers to stroke prevention. These findings have implications for developing more effective strategies for educating African Americans about stroke prevention.

Purpose: The risk for death in patients with retinoblastoma is increased in those who present with metastatic disease, and the role of intensive chemotherapy and autologous hematopoietic stem cell rescue in these patients remains unclear., Design: Nonrandomized interventional case series., Participants: Four consecutive patients with metastatic retinoblastoma., Methods: We treated four patients with retinoblastoma metastatic to the bone and bone marrow with intensive chemotherapy, consolidation with megatherapy, and autologous hematopoietic stem cell rescue. Chemotherapy included courses of carboplatin and etoposide alternating with cyclophosphamide, etoposide, and either carboplatin or cisplatin. Radiation therapy was delivered to areas of bone metastases., Main Outcome Measures: Patient survival., Results: All patients completed and responded to the scheduled therapy; complete response of the bone marrow disease was documented after two courses of chemotherapy in all cases. Two patients are long-term survivors., Conclusions: The treatment described has been successful in obtaining disease-free survival in patients with metastatic retinoblastoma.

Purpose: To evaluate the efficacy of chemoreduction using vincristine and carboplatin in preventing or delaying external-beam radiotherapy (EBRT) or enucleation in patients with intraocular retinoblastoma., Patients and Methods: Twenty-five patients (43 eyes) with newly diagnosed intraocular retinoblastoma received primary treatment with eight courses of vincristine and carboplatin. Focal treatments were delayed until documentation of disease progression. Outcome measures for each eye were length of time to disease progression, avoidance or delay of EBRT, and globe survival. Event-free survival was defined as the length of time to EBRT or enucleation., Results: Disease in all eyes responded to chemotherapy and progressed in only two patients before completion of the eight courses of therapy. Disease in all but four eyes progressed and required focal treatments. Event-free survival estimates at 2 years were 59.2% +/- 12.0% for Reese-Ellsworth group I, II, and III eyes and 26.3% +/- 9.2% for group IV and V eyes. Nineteen eyes (44.2%) required EBRT and 13 eyes (30.2%) were enucleated. The ocular salvage rate was 83.3% for Reese-Ellsworth group I to III eyes and 52.6% for group IV and V eyes. For those patients receiving EBRT, the median time from enrollment to EBRT was 9.5 months (median age at EBRT, 21 months)., Conclusion: In combination with appropriate early intensive focal treatments, chemoreduction with vincristine and carboplatin, without etoposide, may be an alternative treatment for patients with early-stage intraocular retinoblastoma, although additional studies are needed. Patients with advanced intraocular disease require more aggressive treatments.

Purpose: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS)., Patients and Methods: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival., Results: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% +/- 9% and 56% +/- 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% +/- 10%)., Conclusion: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.

Purpose: The purpose of this study was to document the ocular preservation rate after 36 Gy external beam radiation therapy (EBRT) for retinoblastoma., Patients and Methods: Forty-nine eyes of 38 patients were treated with a median dose of 36 Gy EBRT. The patient population included 7 unilateral and 31 bilateral presentations, with a median age at diagnosis of 4 months. Eyes enucleated at the time of diagnosis or treated with other measures were not included in the analysis of ocular preservation. The median age at EBRT was 8 months. Patients were monitored for progression of disease after EBRT and second malignant neoplasms., Results: The median follow-up was 88.6 months, with an estimated ocular preservation rate of 82.0% +/- 5% at 10 years. There was a difference in the ocular preservation rates for patients with advanced disease (Reese-Ellsworth group III-V) compared with early disease. Metastatic disease developed in two patients, and a second malignant neoplasm developed in three. Patients treated with en face electrons experienced a lower 5-year estimate of ocular preservation than those treated with photons, although patients treated with electrons were more likely to have advanced disease., Conclusions: The use of low-dose EBRT (36 Gy) results in ocular preservation rates that are comparable to those of high-dose EBRT. The use of electrons requires careful treatment planning and computerized dosimetry.

Purpose: To report a child with retinoblastoma and Waardenburg syndrome who developed ovarian metastases., Design: Interventional case report., Methods: Unilateral retinoblastoma was diagnosed in a 3-year-old girl with Waardenburg syndrome and leukocoria in the right eye. The patient had a Reese-Ellsworth Group Va tumor and underwent enucleation. Two years later, she developed metastatic disease involving the bone marrow, right humerus, both supraorbital bones, and both tibias. She was treated with chemotherapy, orbital irradiation, and bone marrow transplant but returned 7 months later with back pain and urinary retention., Results: Exploratory laparotomy revealed a right ovarian mass, and the excised ovary showed metastatic retinoblastoma. The child underwent chemotherapy and remained asymptomatic for 9 months, when brain metastases were diagnosed. She died within 2 days of admission., Conclusion: We believe that this is the first description of a patient with retinoblastoma and Waardenburg syndrome and of an ovarian metastasis from retinoblastoma.

Purpose: Standard multiagent chemotherapy for osteosarcoma may include platinum compounds, doxorubicin, and high-dose methotrexate. By identifying new chemotherapeutic strategies, the outcome of these patients can be improved and the toxicity of treatment regimens decreased., Patients and Methods: The authors evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to conventional treatment., Results: Fourteen patients with refractory osteosarcoma were treated with this combination. Twelve patients had been previously treated with a multiagent regimen that included carboplatin, ifosfamide, methotrexate, and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites of relapse included lung, bone, and brain. A total of 47 courses were given. An overall response rate of 28.5% was achieved. A complete response was obtained in one patient (7.1%), a partial response was obtained in three patients (21.4%), and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary form of toxicity observed; the median duration of absolute neurophil count less than 500/microL was 4 days., Conclusions: The combination of cyclophosphamide and etoposide resulted in a response rate of 28.5% in patients with refractory or relapsed osteosarcoma, and its incorporation into front-line therapies deserves further evaluation.

This study characterizes the patterns of abdominal recurrence of Wilms tumor and describes the role of sonography in its detection. Twelve patients who had initial tumor recurrence in the abdomen were evaluated. Five patients had recurrence in the kidney; all had nephrogenic rests detected by computed tomography (CT) or magnetic resonance (MR) imaging but not by sonography. The remaining 7 patients had recurrence in the peritoneum (4), the nephrectomy site (2), or the regional lymph nodes (1); tumor spillage had occurred in five of these patients. Four recurrences were detected during therapy, and eight within 3 years after completion of therapy. Seven of the 12 recurrences were first detected by sonography. All 11 sonograms obtained at the time of relapse showed tumor recurrence. Nine patients died a median of 10 months after relapse. The results suggest that regular sonographic surveillance for 3 years after therapy is likely to reveal most abdominal recurrences. Supplementation with CT or MR imaging is indicated for detection of nephrogenic rests.

Background: Despite improved therapies, 30-40% of patients with Ewing tumors (ET) experience recurrence and have a poor prognosis. The authors analyzed factors prognostic of survival in patients with recurrent ET., Methods: The authors assessed the relation between postrecurrence survival (PRS) and demographic, disease, and treatment factors in 71 patients who experienced recurrent ET after treatment on one of three consecutive institutional protocols., Results: Thirty-four patients (47.9%) had distant recurrence, 25 patients (35.2%) had local recurrence, and 12 patients (16.9%) had both distant and local recurrence at a median of 1.7 years after diagnosis. The probability of 5-year PRS (+/- 1 standard error) was 17.7%+/-4.5%. Recurrence > or = 2 years after diagnosis predicted a significantly better outcome (5-year PRS, 34.9%+/-8.5%) compared with earlier recurrence (5.0%+/-2.8%; P < 0.001). Patients who had both local and distant recurrence fared worse (5-year PRS, 12.5%+/-8.3%) compared with patients who had local recurrence alone (21.7%+/-7.8%) or distant recurrence alone (17.6+/-6.1%). Among patients with local recurrence alone, those who underwent salvage with radical surgery had significantly higher 5-year PRS estimates (31.4%+/-11.6%) compared with the other patients (9.1%+/-6.1%; P = 0.023). Pulmonary irradiation significantly improved the outcomes of patients with isolated pulmonary recurrence (5-year PRS estimate, 30.3%+/-12.5% vs. 16.7%+/-10.8%, respectively; P = 0.018)., Conclusions: Although outcomes are generally poor after patients experience recurrence of ET, certain patient groups differ appreciably in their likelihood of survival. Patients who experience recurrence > or = 2 years after diagnosis and patients who have local recurrence that can be treated with radical surgery and intensive chemotherapy have the most favorable outcomes.

Purpose: To evaluate the efficacy of multiagent chemotherapy in the neoadjuvant treatment of retinoblastoma., Design: Noncomparative, prospective case series., Participants: Twenty consecutive patients with multifocal intraocular retinoblastoma (4 unilateral, 16 bilateral [36 eyes])., Intervention: Eight cycles of chemotherapy with carboplatin and vincristine were administered at 3-week intervals over a 6-month period. Supplemental therapy was withheld until disease progression was documented., Main Outcome Measures: Disease progression (defined as tumor growth, vitreous or subretinal seed progression, and new tumor formation), delay of external beam radiotherapy, and ocular survival., Results: Thirty-six eyes were treated. Eighteen eyes had Reese-Ellsworth group I-III tumors, and 16 eyes had Reese-Ellsworth group IV-V tumors at diagnosis. Two patients, who had unilateral disease at diagnosis, subsequently had tumors develop in the contralateral eye. Nineteen of 20 patients (95%) completed eight cycles of chemotherapy without disease progression. Three eyes of three different patients were successfully treated with chemotherapy alone. Thirty-three of 36 eyes (92%) progressed after completion of chemotherapy: 15 of the 18 eyes (83.3%) with Reese-Ellsworth group I-III and 16 of 16 eyes (100%) with Reese-Ellsworth group IV-V tumors. Seventeen eyes (52%) had growth of a tumor, whereas 14 eyes (42%) had progressive vitreous seeding, and 2 eyes (6%) had new tumors develop. Fifteen eyes (42%) required external beam radiotherapy. Twenty-nine of 36 (80.5%) eyes were salvaged. The median follow-up after chemotherapy was 19 months (range, 3-42 months)., Conclusions: Multiagent chemotherapy alone does not ensure a cure for multifocal intraocular retinoblastoma. Supplemental focal therapy is needed to control disease progression.

Background: The purpose of this article was to evaluate the utility of a pharmacokinetically modeled measure of regional contrast access, based on dynamic contrast-enhanced magnetic resonance imaging (MRI) studies after preoperative chemotherapy, as a predictor of disease free survival in osteosarcoma., Methods: The kinetic parameters of a two-compartment pharmacokinetic model of MRI contrast agent accumulation were analyzed in relation to disease free survival in 31 patients who received protocol-based therapy for nonmetastatic osteosarcoma of the extremities. The modeled exchange rate of contrast between the plasma and the tumor extravascular extracellular fluid space served as a measure of regional contrast access. The prognostic impact of both the clinically accepted standard of histologic evaluation of tumor necrosis and the regional contrast access were analyzed with tumor size as an influential factor., Results: Although the histologic grade of response was not a statistically significant prognostic factor in these patients (P = 0.884), regional contrast access after preoperative chemotherapy was significantly predictive of disease free survival (P = 0.035) in the Cox proportional hazards model. Lower regional access before surgery and smaller tumor size were associated with a better treatment outcome. Log-rank analyses of Kaplan-Meier curves indicated that the impact of regional access was most pronounced in patients with larger tumors (P = 0.052). Higher regional access at presentation also was associated significantly with greater decreases during therapy., Conclusions: Dynamic MRI estimates of regional contrast access after preoperative chemotherapy, when combined with tumor size, holds promise for the early identification of patients at risk of recurrence. The availability of such response predictors could facilitate the development of risk-adapted treatment approaches., (Copyright 2001 American Cancer Society.)

Background: Although the pathologic features and imaging appearance of childhood primary ovarian neoplasms have been well described, little information is available about the malignancies that may secondarily involve the ovary., Objective: To determine the relationship between the imaging features and the histopathology of secondary ovarian neoplasms in children treated at our institution., Materials and Methods: We searched our institutional database for codes indicating metastatic ovarian disease. Of the 35 patients with such codes, 18 had pathologically proven secondary ovarian disease. From their medical records we recorded demographic data, presenting symptoms, and evidence of endocrine dysfunction. We reviewed the pre-oophorectomy imaging and the subsequent pathologic specimens., Results: One-third of the patients had bilateral pelvic masses; another third had large masses indistinguishable from the ovaries. Twelve (67%) had either ascites, peritoneal implants, matted bowel, adenopathy, pleural effusions, or some combination of these. Five (28%) had other metastatic disease. Primary tumors included colon adenocarcinoma (9), Burkitt's lymphoma (3), alveolar rhabdomyosarcoma (3), Wilms' tumor (1), neuroblastoma (1), and retinoblastoma (1)., Conclusion: Although rare, secondary ovarian tumors should be considered in the differential diagnosis of children with ovarian masses. Bilateral ovarian masses or large masses indistinguishable from the ovaries, particularly in the presence of other metastatic foci, may help distinguish primary from secondary ovarian malignancies.

Purpose: We investigated one 201Tl bone scintigraphy method as a predictor of histologic response and event-free survival (EFS) of nonmetastatic extremity osteosarcoma., Materials and Methods: We evaluated images of the primary tumor to determine whether they exhibited a donut of avidity for 40 patients enrolled on a single institutional protocol. Participants underwent three serial 201Tl bone scintigraphy studies during preoperative neoadjuvant chemotherapy. Intra- and interobserver variability of the method was assessed, and the presence of the donut of avidity was examined as a predictor of EFS and histologic response., Results: Fifty-three percent of patients were female and 75% were Caucasian; the median age at diagnosis was 13.5 years. Intraobserver agreement was moderate to very good, ranging from 0.595 to 0.865. Interobserver agreement was moderate to good for all time points, ranging from 0.576 to 0.708. There was a significant difference in EFS among patients with and without the donut-shape at any of the three time points (P = 0.049); patients whose tumors displayed a donutshape had inferior EFS., Conclusion: The pattern of donut avidity in extremity OS is a predictor of lower EFS, but does not correlate with histologic response to therapy.

Background: In children with osteosarcoma who have undergone thoracotomy, it often is difficult to distinguish metastatic from benign recurrent pulmonary nodules. The authors of this study sought to identify any computed tomography (CT) imaging pattern of recurrent pulmonary metastases in this patient population. The authors also sought to identify associated prognostic factors., Methods: CT scans obtained after thoracotomy were available for 35 patients with osteosarcoma who had undergone resection of presumed pulmonary metastases at St. Jude Children's Research Hospital (Memphis, TN). CT scans obtained before the initial thoracotomy were available for 33 of the 35. The authors recorded location, histologic diagnosis, and time of development of the original pulmonary nodules, time of recurrence of pulmonary disease; the location of recurrent nodules, and the presence of calcification, adenopathy, or progressive pleural disease, as well as patient demographic data, survival data, and location of the primary tumor site., Results: Pulmonary nodules recurred in 32 of the 35 patients after thoracotomy. Nineteen of these patients underwent resection of the recurrent lesions and 1 who died underwent an autopsy; 18 of the 20 patients had metastatic disease. The only CT finding consistently associated with recurrent metastatic disease was progressive pleural thickening, which predicted a poor outcome. The occurrence of a solitary pulmonary nodule in the lung contralateral to the previous surgery was associated almost always with a benign process., Conclusions: CT imaging cannot distinguish reliably between benign and metastatic recurrent pulmonary disease after thoracotomy in patients with osteosarcoma. Recurrent pulmonary disease in this set of patients is likely to be metastatic, and aggressive surgical intervention is probably warranted. In this study, patients who had progressive pleural disease after thoracotomy consistently experienced pulmonary metastatic recurrence and had a poor prognosis., (Copyright 2001 American Cancer Society.)

Metastatic osteosarcoma most commonly affects the lungs and other bones. Hepatic metastasis at the time of diagnosis is extremely rare. A 14-year-old boy with synovial sarcoma of the left popliteal fossa was treated with surgical resection, radiotherapy for microscopic residual disease, and 1 year of chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin). Approximately 10 years after the initial diagnosis, a secondary osteosarcoma developed in the left proximal tibia. Computed tomography at presentation showed bilateral pulmonary metastases and large ossified nodules in the liver that demonstrated abnormal avidity on 99mTc MDP bone scan indicating hepatic metastasis. Despite chemotherapy (cisplatin, ifosfamide, high-dose methotrexate, and dacarbazine), the patient died of progressive disease 4 months after the diagnosis of the second cancer. Hepatic metastasis was found at the time of diagnosis of a secondary osteosarcoma and manifested as ossified nodules. The risk of radiation-induced osteosarcoma should always be considered in decisions about treatment for soft-tissue sarcoma.

Ninety-five percent of bone tumors are now managed with limb-sparing techniques. For pediatric patients with bone cancer, such limb reconstruction techniques often involve the placement of large endoprosthetic devices with the goal of improving survivors' quality of life. Nevertheless, few radiologic publications discuss the use of these techniques in children and adolescents. This pictorial essay describes the imaging characteristics of the complications associated with endoprosthetic devices and discusses the conditions that may simulate them.

Purpose: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin., Patients and Methods: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation., Results: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity., Conclusion: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.

Background/purpose: To better characterize childhood carcinoid tumors, the authors reviewed the clinical presentation, treatment, and outcomes of pediatric patients with these rare tumors., Methods: A retrospective review was conducted of medical records and pathologic materials of all children with carcinoid tumors treated at St Jude Children's Research Hospital between December 1977 and March 1999., Results: Eight patients (median age, 12.7 years) were identified; 2 were boys, and 7 were white. Primary tumor sites were the appendix (n = 5), small intestine (n = 1), bronchus (n = 1), and 1 unknown site. In 7 cases, carcinoid tumor was not suspected at the time the tumor was identified. Seven patients had localized disease; 5 remain disease-free after complete resection, and 2, whose carcinoid tumors were identified incidentally, died of metastatic mucinous adenocarcinoma of the colon. One patient who presented with symptoms of carcinoid syndrome had metastatic disease that responded poorly to cytotoxic chemotherapy and remains alive with active disease., Conclusions: Although most pediatric carcinoid tumors arise in the appendix, these tumors also occur in other primary sites. Clinical awareness and early diagnosis are important factors in preventing morbidity and mortality. Outcomes are excellent for patients with localized disease that is completely resected, but those with metastatic disease fare poorly. New therapeutic strategies are needed for these patients.

Background: Bone sarcomas of the head and neck are difficult to resect. The authors reviewed their institutional experience with these tumors to characterize patients' clinical findings and to assess the impact of surgical resection on outcome., Methods: The records of the 28 patients with bone sarcomas originating in the head and neck treated at St. Jude Children's Research Hospital between March 1962 and January 1998 were reviewed., Results: There were 10 males and 18 females (median age, 12.6 years) each with a single sarcoma: osteosarcoma (18), Ewing sarcoma (7), malignant fibrous histiocytoma (MFH) (2), and fibrosarcoma (1). Primary tumor sites included the maxilla (13), skull (10), mandible (2), and other sites (3). All but one patient with Ewing sarcoma had localized disease at the time of diagnosis. All patients underwent surgery: complete resection, 8; gross total resection, 4; incomplete resection, 14; and biopsy only, 2; 22 also received chemotherapy. Radiotherapy was given to all patients with Ewing sarcoma and to four patients with primary osteosarcoma. Twelve patients survived a median of 8.4 years after diagnosis, 14 died of disease, and 2 died of unrelated causes. Local disease progression was evident in 12 patients (9 with osteosarcoma, 2 with MFH, and 1 with Ewing sarcoma) who died of disease, 9 of whom had the initial treatment of biopsy alone or incomplete resection. Patients with osteosarcoma who had the initial treatment of incomplete resection or biopsy alone were more likely to experience local failure (P = 0.001) and had poorer survival (P = 0.014) than those who underwent complete or gross total resection., Conclusions: Bone sarcomas of the head and neck are rare among children and most often are localized at the time of diagnosis. Incomplete resection of osteosarcoma is associated with local failure and poor outcome. Although aggressive surgery is essential for the cure of osteosarcoma, its necessity in the treatment of Ewing sarcomas remains controversial.

Purpose: To identify areas of concern regarding the conduct of phase I trials, the perceived expectations and motivations of the parents of children entered, the expectations of toxicity and benefit, and the ethical concerns of pediatric hematologists and oncologists in the United Kingdom and North America., Methods: A survey instrument consisting of 19 open- and closed-ended questions was sent to United Kingdom Children's Cancer Study Group (UKCCSG)- and Pediatric Oncology Group (POG)-affiliated pediatricians., Results: Fifty-three UKCCSG- and 78 POG-affiliated pediatricians responded. Thirty-two UKCCSG and 51 POG respondents had previously entered at least one child into a phase I study. Overall, respondents believed that parents entered their children for medical benefit, altruism, and hope of cure. Although many respondents believed that children could benefit from medical improvement, feelings of altruism, and maintenance of hope, the chance of cure or complete remission was thought to be small. Similarly, parents were thought to potentially benefit through altruism and maintenance of hope. Whereas 83% of UKCCSG respondents indicated that phase I trials were associated with ethical difficulties, this was a concern for 48% of POG respondents. The main ethical concerns of respondents were risk of toxicity, consent of the child, unrealistic hope, and coercion., Conclusion: The respondents in this survey expressed mainly ethical concerns regarding the conduct of phase I trials and had realistic expectations of the potential for toxicity and benefit for those children who participate in these studies.

Purpose: The aim of this study was to assess renal tubular toxicity (RTT) of ifosfamide-containing regimens (ICR) in patients with newly diagnosed sarcomas at St. Jude Children's Research Hospital., Methods: The authors reviewed the records of 199 patients receiving ICR at St. Jude between June 1986 and December 31, 1994 for evidence of RTT. Their median age was 13.3 years (range 1.2-24.8); 150 patients were white and 112 were male patients. Diagnoses included osteosarcoma (n = 82), Ewing sarcoma (n = 82), rhabdomyosarcoma (n = 28), and a group of other tumors (n = 7)., Results: The authors estimated the proportion of patients with severe RTT during the first five cycles of ICR and within 1 year after therapy for three groups of patients receiving ifosfamide (IFOS, n = 110), ifosfamide/cisplatin (IFOS/CDDP, n = 51), and ifosfamide/carboplatin (IFOS/CARBO, n = 38). The IFOS/CDDP patients received three cycles of IFOS before receiving CDDP and received only 200 mg/m2 by cycle 5, whereas the IFOS/CARBO patients received both agents simultaneously. The authors compared the probability of severe RTT among treatment groups using a generalized linear model for the first five cycles of ICR, as well as the probability of severe RTT within 1 year after therapy among treatment groups for patients receiving all prescribed IFOS using an exact chi-square test with pairwise comparisons when the three-way P value was less than 0.10. The proportion of patients with severe RTT during the first three cycles of ICR was significantly greater in the IFOS/CARBO group than in the other two. Although the proportion of patients with severe RTT in the IFOS/CDDP group increased during cycles 4/5, the proportion of patients with severe RTT remained significantly greater in the IFOS/ CARBO group. Within 1 year after therapy, the proportion of patients with severe RTT differed among the three groups, and pairwise comparisons revealed a significant difference between the IFOS and the IFOS/CDDP group. Severe RTT developed in four IFOS/CDDP patients more than 1 year after therapy, suggesting a long-term effect of CDDP on tubular function., Conclusions: Chemotherapy regimens including IFOS/ CARBO produce severe acute RTT more frequently than regimens including IFOS or IFOS/CDDP. Patients receiving IFOS/ CDDP appear at risk for delayed RTT. Long-term follow-up of these patients is essential to assess whether the number of patients receiving IFOS/CDDP with severe RTT continues to increase over time and to evaluate the long-term significance of these abnormalities.