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  • 1
    In: Neuro-Oncology, 2014, Vol. 16(suppl3), pp.iii24-iii24
    Description: BACKGROUND: Although childhood malignancies have become curable in about 75% of cases due to empirically developed multi-modal therapeutic concepts applied in nation-wide collaborative trials, for children with a relapse, cure remains the exception. In the framework of the ICGC project PedBrain many new potentially druggable genetic lesions have been identified. However, it will not be feasible to conduct traditional phase I trials for all these new drugs in these overall rare entities. To still have our young patients participating in the recent advances in molecular targeted drug treatment, we initiated a novel innovative way of introducing these drugs in a clinical setting based on an individualized molecular rationale, a concept called INFORM (INdividualized therapy For Relapsed Malignancies in childhood). METHODS: Exome- and low-coverage whole-genome sequencing, RNA sequencing, gene expression profiling, DNA methylation profiling, bioinformatic prediction of drug targets and compound selection are carried out aiming at a turnaround time of 4 weeks or less after re-biopsy of the tumor. In the current feasibility phase, drug targets and prioritization are offered to the treating physician in the local hospital for individual treatment decisions. RESULTS: Ten patients were recruited to the INFORM-pilot study by now. For all but two, druggable targets have been identified. The first two patients with early follow-up MRIs after 6 weeks had stable disease (medulloblastoma) and 50% tumor volume reduction (myofibroblastc tumor), respectively. In an additional case with pontine glioma, molecular diagnostics significantly contributed to the establishment of an unambiguous diagnosis. CONCLUSIONS: This is the first population-based study using next-generation sequencing technologies to guide treatment decisions in a clinical setting. In addition to this advance in “next-generation” clinical oncology, INFORM will also reveal the largest comprehensive molecular datasets of relapsed tumors to date, and since primary tumor material from the same patient will also be analyzed whenever available, will likely identify key biological properties of relapsing malignancies and recurrent mechanisms of drug resistance across entities. SECONDARY CATEGORY: Pediatrics.
    Keywords: Pediatrics ; Drug Resistance ; Magnetic Resonance Imaging ; Population Studies ; Oncology ; Tumors ; Children ; Clinical Trials ; Brain Tumors ; Gene Expression ; Malignancy ; RNA ; DNA Methylation ; Medulloblastoma ; Glioma ; Bioinformatics ; Drugs ; Hospitals ; Neurology & Neuropathology;
    ISSN: 1522-8517
    E-ISSN: 1523-5866
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  • 2
    Language: English
    In: Cancer Research, 10/01/2018, Vol.78(19 Supplement), pp.IA11-IA11
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
  • 4
    Language: English
    In: Journal of Obstetric, Gynecologic & Neonatal Nursing, November 2008, Vol.37(6), pp.631-639
    Description: To describe support needs and comfort level of labor nurses caring for families experiencing perinatal loss. Qualitative descriptive study. A western hospital birthing unit. Ten labor nurses. Participants completed online surveys and follow-up interviews; data saturation was reached. Content analysis produced themes and recommendations related to providing perinatal bereavement care. Participants reviewed and confirmed accuracy of the results. Nurses are generally comfortable but find it difficult to provide perinatal bereavement care. Strategies for coping include focusing on needed care, talking to nursing peers, and spending time with their own family members. Nurses take turns providing care depending on “who is best able to handle it that day” and prefer not to be assigned a laboring patient in addition to the grieving parents. Developing clinical expertise is necessary to gain the comfort level and the skills necessary to care for these vulnerable families. Orientation experiences and nursing staff debriefing would help. Needed education includes grief training, communication techniques, and guidelines for the extensive paperwork. Initial and ongoing education of nurses about perinatal bereavement care is needed. Effective strategies for coping during and after providing care would support nurses in meeting the emotional challenge of providing high quality perinatal bereavement care.
    Keywords: Perinatal Loss ; Bereavement ; Coping Strategies ; Grief ; Labor Care ; Medicine ; Nursing
    ISSN: 0884-2175
    E-ISSN: 1552-6909
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  • 5
  • 6
  • 7
    Language: English
    In: Journal of Clinical Oncology, 05/20/2017, Vol.35(15_suppl), pp.10509-10509
    ISSN: 0732-183X
    E-ISSN: 1527-7755
    Source: CrossRef
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  • 8
    Language: English
    In: European Journal of Cancer, September 2016, Vol.65, pp.91-101
    Description: The ‘Individualized Therapy for Relapsed Malignancies in Childhood’ (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of ‘intermediate’ or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase–mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors, and presents a model with considerable interest and practical relevance in the burgeoning era of personalised medicine.
    Keywords: Personalised Medicine ; Oncology ; Paediatrics ; Precision Medicine ; Molecular Targeted Therapy ; Deep Sequencing ; Cancer ; Sarcoma ; Brain ; Medicine
    ISSN: 0959-8049
    E-ISSN: 1879-0852
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  • 9
    Language: English
    In: Western Journal of Nursing Research, November 2013, Vol.35(10), pp.1266-1279
    Description: Cardiovascular disease (CVD) is the leading cause of death for women, and disproportionally so for African American and Latina women. CVD is largely preventable and many risks can be attributable to health behaviors, implementing and sustaining positive health behaviors is a challenge. Motivational interviewing is one promising intervention for initiating behavior change. The purpose of this review was to identify, synthesize, and critically analyze the existing literature on the use of motivational interviewing as a behavioral intervention to reduce CVD risk among African American and Latina women. Seven studies were identified that met inclusion criteria. Results of this review suggest that motivational interviewing has mixed results when used to reduce cardiovascular risk factors in African American and Latina women. More research using a standardized motivational interviewing approach is needed to definitively determine if it is an effective behavioral intervention to reduce CVD risk when used in populations of African American and Latina women.
    Keywords: Cardiovascular Disease ; Women ; African American ; Hispanic ; Latina ; Motivational Interviewing ; Nursing ; Public Health
    ISSN: 0193-9459
    E-ISSN: 1552-8456
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  • 10
    In: Brain Pathology, July 2016, Vol.26(4), pp.506-516
    Description: The “pediatric targeted therapy” (PTT) program aims to identify the presence and activity of druggable targets and evaluate the clinical benefit of a personalized treatment approach in relapsed or progressive tumors on an individual basis. 10 markers (HDAC2, HR23B, p‐AKT, p‐ERK, p‐S6, p‐EGFR, PDGFR‐alpha/beta, p53 and BRAFV600E) were analyzed by immunohistochemistry. Pediatric patients with tumors independent of the histological diagnosis, with relapse or progression after treatment according to standard protocols were included.  = 61/145 (42%) cases were eligible for analysis between 2009 and 2013, the most common entities being brain tumors. Immunohistochemical stainings were evaluated by the ‐Score (0–300). In 93% of the cases potentially actionable targets were identified. The expressed or activated pathways were histone deacetylase (HDACs; 83.0% of cases positive), EGFR (87.2%), PDGFR (75.9%), p53 (50.0%), MAPK/ERK (43.3%) and PI3K/mTOR (36.1%). Follow‐up revealed partial or full implementation of PTT results in treatment decision‐making in 41% of the cases. Prolonged disease stabilization responses in single cases were noticed, however, response rates did not differ from cases treated with other modalities. Further studies evaluating the feasibility and clinical benefit of personalized diagnostic approaches using paraffin material are warranted.
    Keywords: Brain Tumors ; Pediatric Oncology ; Personalized Medicine ; Targeted Therapy ; Relapsed Childhood Tumors ; Predictive Markers
    ISSN: 1015-6305
    E-ISSN: 1750-3639
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