Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis.
Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority.
In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.
The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary effort to develop new standardized response criteria for clinical trials in brain tumors. The RANO group identified knowledge gaps relating to the definitions of tumor response and progression after the use of surgical or surgically based treatments.
OBJECTIVE: To outline a proposal for new response and progression criteria for the assessment of the effects of surgery and surgically delivered therapies for patients with gliomas.
METHODS: The Surgery Working Group of RANO identified surgically related end-point evaluation problems that were not addressed in the original Macdonald criteria, performed an extensive literature review, and used a consensus-building process to develop recommendations for how to address these issues in the setting of clinical trials.
RESULTS: Recommendations were formulated for surgically related issues, including imaging changes associated with surgical resection or surgically mediated adjuvant local therapies, the determination of progression in the setting where all enhancing tumor has been removed, and how new enhancement should be interpreted in the setting where local therapies that are known to produce nonspecific enhancement have been used. Additionally, the terminology used to describe the completeness of surgical resections has been recognized to be inconsistently applied to enhancing vs nonenhancing tumors, and a new set of descriptors is proposed.
CONCLUSION: The RANO process is intended to produce end-point criteria for clinical trials that take into account the effects of prior and ongoing therapies. The RANO criteria will continue to evolve as new therapies and technologies are introduced into clinical trial and/or practice.
Not uncommonly, spine surgeons and physiatrists note a mismatch between patient-reported outcome measures, where one measure might indicate a good outcome and another indicates an inferior outcome after spine treatment. This may be the result of patient characteristics that lead to changes in internal standards, values, and conceptualization of their own health-related quality of life. This can result in a ‘‘moving goal post’’ when a self-report outcome measure is used for prepost comparisons. These ‘‘response shifts’’ may obfuscate relevant changes of interest to clinicians and are meaningful and worthy of study in and of themselves.
PURPOSE: To provide a background on response shift with an emphasis on distinctions relevant to spinal interventions, both surgical and nonsurgical. To describe current methods for detecting and investigating response shift phenomena, and to propose specific hypotheses that can be tested in collaborative research. METHODS AND RESULTS: Two types of methods will be briefly described: methods that require new data collection; and methods that use recent statistical and technical advances to implement secondary analysis of existing data. Two specific testable hypotheses for spinal disorders are suggested along with suggested methods for testing these hypotheses. CONCLUSIONS: A response shift will cause the patient to use the same functional outcome report measure differently pre- and posttreatment. Response shift phenomena are likely to affect the measurement properties of standard spine outcome measures and to obfuscate differences between treatments in clinical trials and cost-effectiveness studies. They point to a need for developing strategies in clinical practice to manage response shifts so that they enhance patient well-being.
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