The role of chemotherapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

TARGET POPULATION: This recommendation applies to adults with newly diagnosed brain metastases; however, the recommendation below does not apply to the exquisitely chemosensitive tumors, such as germinomas metastatic to the brain. RECOMMENDATION: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT)? Level 1 Routine use of chemotherapy following WBRT for brain metastases has not been shown to increase survival and is not recommended. Four class I studies examined the role of carboplatin, chloroethylnitrosoureas, tegafur and temozolomide, and all resulted in no survival benefit. Two caveats are provided in order to allow the treating physician to individualize decision-making: First, the majority of the data are limited to non small cell lung (NSCLC) and breast cancer; therefore, in other tumor histologies, the possibility of clinical benefit cannot be absolutely ruled out. Second, the addition of chemotherapy to WBRT improved response rates in some, but not all trials; response rate was not the primary endpoint in most of these trials and end-point assessment was non-centralized, non-blinded, and post-hoc. Enrollment in chemotherapy-related clinical trials is encouraged

Recent patterns in chronic disease mortality in remote living Indigenous Australians

Background: Despite the well-recognised Indigenous-non-Indigenous health disparity, some reports suggest improvements in Indigenous mortality. Our aim was to quantify Indigenous mortality in Outer Regional (OR), Remote (R), and Very Remote (VR) areas in New South Wales, Queensland, South Australia, Western Australia, and the Northern Territory and changes in mortality from 1998 to 2005

The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline

QUESTION: Should patients with newly-diagnosed metastatic brain tumors undergo open surgical resection versus whole brain radiation therapy (WBRT) and/or other treatment modalities such as radiosurgery, and in what clinical settings? TARGET POPULATION: These recommendations apply to adults with a newly diagnosed single brain metastasis amenable to surgical resection. RECOMMENDATIONS: Surgical resection plus WBRT versus surgical resection alone Level 1 Surgical resection followed by WBRT represents a superior treatment modality, in terms of improving tumor control at the original site of the metastasis and in the brain overall, when compared to surgical resection alone. Surgical resection plus WBRT versus SRS + or - WBRT Level 2 Surgical resection plus WBRT, versus stereotactic radiosurgery (SRS) plus WBRT, both represent effective treatment strategies, resulting in relatively equal survival rates. SRS has not been assessed from an evidence-based standpoint for larger lesions (\u3e3 cm) or for those causing significant mass effect (\u3e1 cm midline shift). Level 3 Underpowered class I evidence along with the preponderance of conflicting class II evidence suggests that SRS alone may provide equivalent functional and survival outcomes compared with resection + WBRT for patients with single brain metastases, so long as ready detection of distant site failure and salvage SRS are possible. Note The following question is fully addressed in the WBRT guideline paper within this series by Gaspar et al. Given that the recommendation resulting from the systematic review of the literature on this topic is also highly relevant to the discussion of the role of surgical resection in the management of brain metastases, this recommendation has been included below

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Distances walked in the six-minute walk test: suggestion of defining characteristic for the nursing diagnosis Ineffective Peripheral Tissue Perfusion Distancias recorridas en la prueba de caminata de los seis minutos: propuesta de característica definitoria para el diagnóstico de enfermería Perfusión Tisular Periférica Inefectiva Distâncias percorridas no teste de caminhada de seis minutos: proposta de característica definidora para o diagnóstico de enfermagem Perfusão Tissular Periférica Ineficaz

Distances walked in walking tests are important functional markers, although they are not accepted as defining characteristics of Ineffective Peripheral Tissue Perfusion. The aims of this study were to verify the distances participants with and without this nursing diagnosis walked in the six-minute walk test and if these measures may be considered defining characteristics of this phenomenon. Participants with (group A; n=65) and without (group B; n=17) this nursing diagnosis were evaluated regarding physical examination, vascular function and functional capacity. Participants of group A seemed to have worse vascular function and functional capacity compared with those of group B. Pain-free travelled distance was predictive of the nursing diagnosis. These results are important for the refinement of this diagnosis. In conclusion, this study provides evidences that the distances walked in the six-minute walk test may be considered defining characteristics of Ineffective Peripheral Tissue Perfusion.<br>Las distancias en pruebas de marcha son importantes marcadores funcionales, pero no son aceptados como características de definición de la Perfusión Tisular Periférica Inefectiva. Los objetivos fueron determinar las distancias recorridas en la prueba de caminata de los seis minutos por los participantes con e sin el diagnóstico de enfermería y si esas medidas se pueden considerar características de definición de este fenómeno. Los participantes con (grupo A, n=65) y sin (grupo B, n=17) el diagnóstico fueron evaluados mediante examen físico, función vascular periférica y capacidad funcional. Los participantes del grupo A ha presentado peor función vascular y desempeño en la prueba de marcha do que aquellos del grupo B. La distancia recorrida libre de dolor fue predictiva del diagnóstico de enfermería. Los resultados de este estudio pueden contribuir para el refinamiento de este diagnóstico. Las distancias recorridas en la prueba de marcha se pueden considerar características de definición de este diagnóstico.<br>Distâncias percorridas em testes de marcha são importantes marcadores funcionais, porém, não são aceitos como características definidoras de Perfusão Tissular Periférica Ineficaz. Os objetivos foram verificar as distâncias percorridas no teste de caminhada de seis minutos, por participantes com e sem esse diagnóstico de enfermagem, e se tais medidas podem ser consideradas características definidoras desse fenômeno. A amostra foi composta por sujeitos com (grupo A, n=65) e sem (grupo B, n=17) Perfusão Tissular Periférica Ineficaz, avaliados quanto ao exame físico, à função vascular periférica e à capacidade funcional. Os participantes do grupo A apresentaram pior função vascular e capacidade funcional do que os do grupo B. Verificou-se que a distância percorrida livre de dor foi preditiva para a ocorrência do diagnóstico de enfermagem. Os resultados deste estudo são importantes para o refinamento desse diagnóstico. Conclui-se que as distâncias percorridas no teste de caminhada de seis minutos podem ser características definidoras de Perfusão Tissular Periférica Ineficaz