Mutational Activation of ras Genes is Absent in Pediatric Osteosarcoma

Activation of ras oncogenes is found in human cancers; overall it is observed in 15% of all neoplasms. The purpose of this study was to assess the extent of involvement of ras oncogenes in osteosarcoma. Tumor samples from a series of 49 pediatric patients diagnosed with osteosarcoma and treated at our institution were evaluated. Paraffin-embedded tumor samples from diagnostic biopsies, from tumor en bloc resection tissue after neoadjuvant chemotherapy, and samples from metastases were examined in search of point mutations in H, K, and N-ras genes at codons 12 and 61 by means of polymerase chain reaction (PCR), slot-blotting, and radioactive labeled specific DNA probes. A total of 92 archival samples were studied. No point mutations activating these genes were found. These findings suggest that the activation by point mutations at codons 12 and 61 of the H, K, and N-ras genes does not play a role in the pathogenesis of human osteosarcoma. Since no point mutations in codons 12 and 61 were detected, it was not possible to establish any correlation between the ras genes and clinical or histologic finding

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisciplinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6-20 MeV electron beams. The median follow-up time for the entire group is 25 months (2-65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT

Impact of PEWS on Perceived Quality of Care During Deterioration in Children With Cancer Hospitalized in Different Resource-Settings

BackgroundChildren with cancer are at high risk for clinical deterioration and subsequent mortality. Pediatric Early Warning Systems (PEWS) have proven to reduce the frequency of clinical deterioration in hospitalized patients. This qualitative study evaluates provider perspectives on the impact of PEWS on quality of care during deterioration events in a high-resource and a resource-limited setting.MethodsWe conducted semi-structured interviews with 83 healthcare staff (nurses, pediatricians, oncology fellows, and intensivists) involved in recent deterioration events at two pediatric oncology hospitals of different resource levels: St. Jude Children’s Research Hospital (SJCRH; n = 42) and Unidad Nacional de Oncología Pediátrica (UNOP; n = 41). Interviews were conducted in the participant’s native language (English or Spanish), translated into English, and transcribed. Transcripts were coded and analyzed inductively.ResultsProviders discussed both positive and negative perspectives of clinical deterioration events. Content analysis revealed “teamwork,” “experience with deterioration,” “early awareness,” and “effective communication” as themes associated with positive perception of events, which contributed to patient safety. Negative themes included “lack of communication,” “inexperience with deterioration,” “challenges with technology”, “limited material resources,” “false positive score,” and “objective tool.” Participants representing all disciplines across both institutions shared similar positive opinions. Negative opinions, however, differed between the two institutions, with providers at UNOP highlighting limited resources while those at SJCRH expressing concerns about technology misuse.ConclusionProviders that care for children with cancer find PEWS valuable to improve the quality of hospital care, regardless of hospital resource-level. Identified challenges, including inadequate critical care resources and challenges with technology, differ by hospital resource-level. These findings build on growing data demonstrating the positive impact of PEWS on quality of care and encourage wide dissemination of PEWS in clinical practice

Mapping Pediatric Oncology Clinical Trial Collaborative Groups on the Global Stage

The global pediatric oncology clinical research landscape, particularly in Central and South America, Africa, and Asia, which bear the highest burden of global childhood cancer cases, is less characterized in the literature. Review of how existing pediatric cancer clinical trial groups internationally have been formed and how their research goals have been pursued is critical for building global collaborative research and data-sharing efforts, in line with the WHO Global Initiative for Childhood Cancer. METHODS: A narrative literature review of collaborative groups performing pediatric cancer clinical research in each continent was conducted. An inventory of research groups was assembled and reviewed by current pediatric cancer regional and continental leaders. Each group was narratively described with identification of common structural and research themes among consortia. RESULTS: There is wide variability in the structure, history, and goals of pediatric cancer clinical trial collaborative groups internationally. Several continental regions have longstanding endogenously-formed clinical trial groups that have developed and published numerous adapted treatment regimens to improve outcomes, whereas other regions have consortia focused on developing foundational database registry infrastructure supported by large multinational organizations or twinning relationships. CONCLUSION: There cannot be a one-size-fits-all approach to increasing collaboration between international pediatric cancer clinical trial groups, as this requires a nuanced understanding of local stakeholders and resources necessary to form partnerships. Needs assessments, performed either by local consortia or in conjunction with international partners, have generated productive clinical trial infrastructure. To achieve the goals of the Global Initiative for Childhood Cancer, global partnerships must be sufficiently granular to account for the distinct needs of each collaborating group and should incorporate grassroots approaches, robust twinning relationships, and implementation science

Sustainable care for children with cancer: a Lancet Oncology Commission.

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020-50 would be four times greater than the cumulative treatment costs of$594 billion, producing a net benefit of $1986 billion on the global investment: a net return of$3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths

Pediatric Oncology in countries with limited resources

Fil: Ribeiro, Raúl C.. St. Jude Children's Research Hospital; Estados UnidosFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arora,Ramandeep. No especifíca;Fil: Antillon, Federico. No especifíca;Fil: Kruger, Mariana. Stellenbosch University; SudáfricaFil: Barr, Ronald D.. McMaster University; Canad

Evolución de los niños tratados por leucemia linfoblástica aguda recidivante en América Central

Background. Outcomes for relapsed childhood acute lymphoblastic leukemia (ALL) have not been documented in resource-limited settings. This study examined survival after relapse for children with ALL in Central America. Methods. A retrospective cohort study was performed and included children with first relapse of ALL in Guatemala, Honduras, or El Salvador between 1990 and 2011. Predictors of subsequent eventfree survival (EFS) and overall survival (OS) were examined. Results. There were 755 children identified with relapsed disease. The median time from diagnosis to relapse was 1.7 years (interquartile range, 0.8-3.1 years). Most relapses occurred during (53.9%) or following (24.9%) maintenance chemotherapy, and the majority occurred in the bone marrow (63.1%). Following the initial relapse, subsequent 3-year EFS (± standard error) and OS were 22.0% ± 1.7%, and 28.2% ± 1.9%, respectively. In multivariable analysis, worse post relapse survival was associated with age ± 10 years, white blood cell count ± 50 ± 109/L, and positive central nervous system status at the original ALL diagnosis, relapse that was not isolated central nervous system or testicular, and relapse < 36 months following diagnosis. Site and time to relapse were used to identify a favorable risk group whose 3-year EFS and OS were 50.0% ± 8.9% and 68.0% ± 8.1%, respectively. Conclusions. Prognosis after relapsed ALL in Central America is poor, but a substantial number of those with favorable risk features have prolonged survival, despite lack of access to stem cell transplantation. Stratification by risk factors can guide therapeutic decision-making.Fondo. Los resultados de la leucemia linfoblástica aguda (LLA) infantil en recaída no se han documentado en entornos de recursos limitados. Este estudio examinó la supervivencia después de la recaída en niños con LLA en América Central. Métodos. Se realizó un estudio de cohorte retrospectivo e incluyó niños con primera recaída de LLA en Guatemala, Honduras o El Salvador entre 1990 y 2011. Se examinaron los predictores de supervivencia libre de eventos (SSC) y supervivencia general (SG) subsiguientes. Resultados. Hubo 755 niños identificados con enfermedad recidivante. La mediana de tiempo desde el diagnóstico hasta la recaída fue de 1,7 años (rango intercuartílico, 0,8-3,1 años). La mayoría de las recaídas ocurrieron durante (53,9 %) o después (24,9 %) de la quimioterapia de mantenimiento, y la mayoría ocurrió en la médula ósea (63,1 %). Después de la recaída inicial, la SSC (± error estándar) y la SG posteriores a los 3 años fueron de 22,0 % ± 1,7 % y 28,2 % ± 1,9 %, respectivamente. En el análisis multivariable, la peor supervivencia posterior a la recaída se asoció con la edad ± 10 años, el recuento de glóbulos blancos ± 50 ± 109/l y el estado positivo del sistema nervioso central en el diagnóstico original de LLA, recaída que no fue del sistema nervioso central aislada o testicular, y recaída < 36 meses después del diagnóstico. El sitio y el tiempo hasta la recaída se usaron para identificar un grupo de riesgo favorable cuya SSC y SG a 3 años fueron 50,0 % ± 8,9 % y 68,0 % ± 8,1 %, respectivamente. Conclusiones. El pronóstico después de la LLA recidivante en América Central es malo, pero un número considerable de personas con características de riesgo favorables tienen una supervivencia prolongada, a pesar de la falta de acceso al trasplante de células madre. La estratificación por factores de riesgo puede orientar la toma de decisiones terapéuticas

La investigación en oncología pediátrica en países de bajos ingresos: conceptos éticos y desafíos

Uneven strides in research and care have led to discrepancies in childhood cancer outcomes between high and low income countries (LICs). Collaborative research may help improve outcomes in LICs by generating knowledge for local scientific communities, augmenting knowledge translation, and fostering context-specific evaluation of treatment protocols. However, the risks of such research have received little attention. This paper investigates the relationship between pediatric oncology research in LICs and four core issues in the ethics literature: standard of care, trial benefits, ethics review, and informed consent. Our aims are to highlight the importance of this field and the need for further inquiry. Pediatr Blood Cancer 2012; 58:492–497.Los avances desiguales en la investigación y la atención han dado lugar a discrepancias en los resultados del cáncer infantil entre los países de ingresos altos y bajos (LIC). La investigación colaborativa puede ayudar a mejorar los resultados en los países de ingreso bajo al generar conocimiento para las comunidades científicas locales, aumentar la traducción del conocimiento y fomentar la evaluación de los protocolos de tratamiento en contextos específicos. Sin embargo, los riesgos de tal investigación han recibido poca atención. Este artículo investiga la relación entre la investigación en oncología pediátrica en los países de ingresos bajos y cuatro temas centrales en la literatura sobre ética: estándar de atención, beneficios del ensayo, revisión ética y consentimiento informado. Nuestros objetivos son resaltar la importancia de este campo y la necesidad de una mayor investigación. Pediatr Blood Cancer 2012; 58:492–497

The evolution of parents’ beliefs about childhood cancer during diagnostic communication: a qualitative study in Guatemala

Introduction Fatalistic cancer beliefs may contribute to delayed diagnosis and poor outcomes, including treatment abandonment, for children with cancer. This study explored Guatemalan parents’ cancer beliefs during initial paediatric cancer communication, and the sociocultural and contextual factors that influence these beliefs.Methods Twenty families of children with cancer were included in this study. We audio-recorded psychosocial conversations with psychologists and diagnostic conversations with oncologists, then conducted semi-structured interviews with parents to explore the evolution of their cancer beliefs. Audio-recordings were transcribed and translated from Spanish into English, with additional review in both languages by bilingual team members. All 60 transcripts were thematically analysed using a priori and novel codes.Results Guatemalan parents’ beliefs evolve as they learn about cancer through various sources. Sources of information external to the cancer centre, including prior experiences with cancer, media exposure, community discussion and clinical encounters, contribute to pre-existing beliefs. Many parents’ pre-existing cancer beliefs are fatalistic; some are influenced by Mayan spirituality. Sources internal to the cancer centre include psychologists and oncologists, other providers, other patients and families. Psychologists acknowledge pre-existing beliefs and deliver cancer education using verbal explanations and hand-drawings. Oncologists provide diagnostic information and outline treatment plans. Both support hope by providing a path toward cure. Parents’ lived experience is a culmination of sources and simultaneously independent. Ultimately most parents arrive at an understanding of cancer that is consistent with an allopathic medical model and offers optimism about outcomes.Conclusion An interdisciplinary communication process that includes cancer education, is attentive to pre-existing beliefs, and supports hope may encourage acceptance of the allopathic medical model and need for treatment. Providers in settings of all resource levels may be able to use these techniques to support cross-cultural cancer communication, reduce treatment abandonment and improve therapy adherence