RESUMO
BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a rare, but lethal pediatric brain tumor with a median survival of less than 1 year. Existing treatment may prolong life and control symptoms, but may cause toxicity and side effects. In order to improve child- and family-centered care, we aimed to better understand the treatment decision-making experiences of parents, as studies on this topic are currently lacking. PROCEDURE: The data for this study came from 24 semistructured interviews with parents whose children were diagnosed with DIPG in two children's hospitals in Switzerland and died between 2000 and 2016. Analysis of the dataset was done using reflexive thematic analysis. RESULTS: For most parents, the decision for or against treatment was relatively straightforward given the fatality of the tumor and the absence of treatment protocols. Most of them had no regrets about their decision for or against treatment. The most distressing factor for them was observing their child's gradual loss of independence and informing them about the inescapability of death. To counter this powerlessness, many parents opted for complementary or alternative medicine in order to "do something." Many parents reported psychological problems in the aftermath of their child's death and coping strategies between mothers and fathers often differed. CONCLUSION: The challenges of DIPG are unique and explain why parental and shared decision-making is different in DIPG compared to other cancer diagnoses. Considering that treatment decisions shape parents' grief trajectory, clinicians should reassure parents by framing treatment decisions in terms of family's deeply held values and goals.
Assuntos
Astrocitoma , Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Neoplasias do Tronco Encefálico/terapia , Humanos , Pais/psicologia , Pesquisa QualitativaRESUMO
IMPORTANCE OF THE FIELD: Antiangiogenic strategies are affording considerable interest and have become a major milestone in therapeutics of various adult cancers. However, progress has been slow to expand such therapies to patients with pediatric solid malignancies. AREAS COVERED IN THIS REVIEW: This review discusses the principal pathways for angiogenesis in pediatric solid malignancies and summarizes recent preclinical and clinical data on antiangiogenesis strategies in these tumors. WHAT THE READER WILL GAIN: The reader will gain state-of-the-art knowledge in the current advancements of antiangiogenic therapies in pediatric clinical trials in regard to supporting preclinical data, and in the status of potential biomarkers investigated for monitoring angiogenesis inhibitors. Mechanisms of resistance to antiangiogenic therapy will also be discussed. Finally, we describe our experience in the monitoring of circulating endothelial cells and progenitors and their potential role as biomarkers of metastatic disease and resistance to antiangiogenic therapies. TAKE HOME MESSAGE: Evaluation and development of antiangiogenesis protocols are starting and represent a crucial step in the management of pediatric solid malignancies today. Emphasis should be placed on the development of proper surrogate markers to monitor antiangiogenic activity and on the possible long-term effects of these therapies in a pediatric population.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Animais , Biomarcadores/análise , Movimento Celular/efeitos dos fármacos , Criança , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos dos fármacos , Humanos , Neovascularização Patológica/sangue , Neovascularização Patológica/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismoAssuntos
Hemangioma/congênito , Doenças do Prematuro/terapia , Neoplasias Cutâneas/congênito , Criança , Pré-Escolar , Terapia Combinada , Estudos Transversais , Criocirurgia , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Estética , Feminino , Hemangioma/diagnóstico , Hemangioma/terapia , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/diagnóstico , Terapia com Luz de Baixa Intensidade , Masculino , Prednisolona/administração & dosagem , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , SíndromeRESUMO
Neuroblastoma (NB) expresses the tyrosine kinase receptors c-Kit, PDGFR-alpha and -beta-targets for STI-571. We investigated a possible combination therapy of STI-571 with retinoic acid (RA) and gamma-irradiation on NB cell viability in vitro. Expression of tyrosine kinase receptors and their ligands was examined in 6 NB cell lines by RT-PCR and FACS. The effect on cell viability was determined by MTT assay. Cell viability of all 6 NB cell lines was significantly inhibited after treatment with 20 microM STI-571 for 72h, two cell lines responding already to 10 microM. Cell lines responded irrespective of their mRNA status or cell surface expression of c-Kit, PDGFR-alpha and -beta. Co-incubation with 9-cis RA sensitized cells to the inhibitory effects of STI-571. However, pre-treatment with 9-cis RA resulted in resistance of NB cell lines to STI-571 and gamma-irradiation. Treatment of NB with STI-571 in combination with 9-cis RA might be a therapeutic strategy for patients in consolidation therapy who have completed gamma-irradiation therapy.