scholarly journals ALK inhibitors, resistance development, clinical trials

2018 ◽  
Vol 25 ◽  
pp. 59 ◽  
Author(s):  
J.M. Rothenstein ◽  
N. Chooback
Keyword(s):  
Clinical Trials ◽  
Patient Outcomes ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Current Treatment ◽  
Resistance Development ◽  
Ongoing Research ◽  
Alk Positive ◽  
Emergence Of Resistance ◽  
Key Questions

The treatment of advanced non-small-cell lung cancer (nsclc) has undergone a paradigm shift since the early 2000s. The identification of molecular subtypes of the disease, based on oncogenic drivers, has led to the development of personalized medicine and the ability to deliver molecularly targeted therapies to patients. In the 10 years that have elapsed since the discovery of the ALK gene in a patient with nsclc, several active drugs have moved rapidly from bench to bedside, and multiple others are currently in clinical trials. Those developments have led to important improvements in patient outcomes, while simultaneously raising key questions about the optimal treatment for ALK-positive nsclc. The inevitable emergence of resistance to alk-directed therapy is central to ongoing research and daily clinical practice for affected patients. In the present review, we highlight the current treatment landscape, the available and emerging clinical trials, and the evolving clinical decision-making in ALK-positive nsclc, with a focus on Canadian practice.

Beyond the Development of Health-Related Quality-of-Life (HRQOL) Measures: A Checklist for Evaluating HRQOL Outcomes in Cancer Clinical Trials—Does HRQOL Evaluation in Prostate Cancer Research Inform Clinical Decision Making?

2003 ◽  
Vol 21 (18) ◽  
pp. 3502-3511 ◽  
Author(s):  
Fabio Efficace ◽  
Andrew Bottomley ◽  
David Osoba ◽  
Carolyn Gotay ◽  
Henning Flechtner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Clinical Trials ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Cancer Clinical Trials ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related

Purpose: The aim of this study was to evaluate whether the inclusion of health-related quality of life (HRQOL), as a part of the trial design in a randomized controlled trial (RCT) setting, has supported clinical decision making for the planning of future medical treatments in prostate cancer. Materials and Methods: A minimum standard checklist for evaluating HRQOL outcomes in cancer clinical trials was devised to assess the quality of the HRQOL reporting and to classify the studies on the grounds of their robustness. It comprises 11 key HRQOL issues grouped into four broader sections: conceptual, measurement, methodology, and interpretation. Relevant studies were identified in a number of databases, including MEDLINE and the Cochrane Controlled Trials Register. Both their HRQOL and traditional clinical reported outcomes were systematically analyzed to evaluate their consistency and their relevance for supporting clinical decision making. Results: Although 54% of the identified studies did not show any differences in traditional clinical end points between treatment arms and 17% showed a difference in overall survival, 74% of the studies showed some difference in terms of HRQOL outcomes. One third of the RCTs provided a comprehensive picture of the whole treatment including HRQOL outcomes to support their conclusions. Conclusion: A minimum set of criteria for assessing the reported outcomes in cancer clinical trials is necessary to make informed decisions in clinical practice. Using a checklist developed for this study, it was found that HRQOL is a valuable source of information in RCTs of treatment in metastatic prostate cancer.

Topical Review: Enhancing Understanding of the Clinical Meaningfulness of Outcomes to Assess Treatment Benefit from Psychological Therapies for Children with Chronic Pain

2019 ◽  
Author(s):  
Tonya M Palermo ◽  
Susmita Kashikar-Zuck ◽  
Anne Lynch-Jordan
Keyword(s):  
Chronic Pain ◽  
Clinical Trials ◽  
Clinical Significance ◽  
Clinical Decision Making ◽  
Psychological Treatment ◽  
Clinical Decision ◽  
Health Impact ◽  
Treatment Benefit ◽  
Topical Review ◽  
Pediatric Chronic Pain

Abstract Objective Despite the availability of measures for assessing physical, psychological, and health impact in children with chronic pain, there are not established guidelines for interpretation of children’s pain outcomes following psychological treatment. The purpose of this topical review is to discuss clinical significance as a neglected area of consideration in pediatric chronic pain assessment and to make recommendations on how the field can move toward benchmarking on core outcome domains. Method We review definitions of clinical significance and examples of several methodologies that have been used in other populations or are emerging in pediatric chronic pain including anchor-based methods, distribution-based methods, or multimethod approaches. Results Few measures across pediatric chronic pain outcome domains have established clinical significance of scores to interpret meaningful change following treatment limiting the interpretability of findings from clinical trials. In the context of clinical practice, several efforts to examine clinical significance to improve the translation of evidence-based measurement into standard clinical decision-making exist. Conclusions Recommendations are provided to encourage additional validation efforts of outcome measures in pediatric chronic pain and to encourage authors to report clinical significance in clinical trials of psychological interventions for pediatric chronic pain.

scholarly journals JAK2 (and other genes) be nimble with MPN diagnosis, prognosis, and therapy

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 110-117 ◽  
Author(s):  
Michele Ciboddo ◽  
Ann Mullally
Keyword(s):  
Clinical Decision Making ◽  
Phenotypic Diversity ◽  
Myeloproliferative Neoplasms ◽  
Clinical Decision ◽  
Prognostic Models ◽  
Driver Mutations ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
Substantial Progress ◽  
Made In

Abstract Now that the spectrum of somatic mutations that initiate, propagate, and drive the progression of myeloproliferative neoplasms (MPNs) has largely been defined, recent efforts have focused on integrating this information into clinical decision making. In this regard, the greatest progress has been made in myelofibrosis, in which high-molecular-risk mutations have been identified and incorporated into prognostic models to help guide treatment decisions. In this chapter, we focus on advances in 4 main areas: (1) What are the MPN phenotypic driver mutations? (2) What constitutes high molecular risk in MPN (focusing on ASXL1)? (3) How do we risk-stratify patients with MPN? And (4) What is the significance of molecular genetics for MPN treatment? Although substantial progress has been made, we still have an incomplete understanding of the molecular basis for phenotypic diversity in MPN, and few rationally designed therapeutic approaches to target high-risk mutations are available. Ongoing research efforts in these areas are critical to understanding the biological consequences of genetic heterogeneity in MPN and to improving outcomes for patients.

A community-based program for personalized cancer care using next-generation sequencing (NGS).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11102-11102
Author(s):  
Shile Liang ◽  
Pranil Chandra ◽  
Zeqiang Ma ◽  
Debbie Haynes ◽  
James Prescott ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Molecular Profiling ◽  
Targeted Agents ◽  
Community Based ◽  
Off Label ◽  
Molecular Abnormalities ◽  
Tumor Types

11102 Background: Despite growing interest and need, molecular profiling of tumor samples is largely unavailable in community cancer centers, where nearly 80% of cancer patients (pts) are treated. In 10/12, Sarah Cannon Research Institute (SCRI) launched a community-based molecular profiling program to: 1) better understand the molecular constituency of cancer patients, 2) identify appropriate pts for phase I and II clinical trials of targeted agents, and 3) identify pts with molecular abnormalities responsive to FDA-approved agents. Methods: Eligible pts consented to testing of available biospecimens, which were interrogated for alterations in 35 cancer-related genes using NGS (1000X average coverage) in a CLIA/CAP laboratory. Results were reported to the treating physician within 14 days and stored in a database to enable correlation with clinical outcomes. Results: As of 1/13, 209 pts had been enrolled with 84% having sufficient material for assay. At least 1 mutation was detected in 46% of tumors. Results in the 3 most commonly assayed tumor types are summarized (Table). Mutations for which there are FDA-approved targeted agents were found in 14 off-label tumors (EGFR 4, KIT 3, SMO 3, BRAF 2, HER2 2). 40 pts (27%) were subsequently enrolled in clinical trials; in 19 of these, assay results influenced clinical trial selection. Conclusions: This program provides molecular profiling data to community oncologists for clinical decision making. Experience to date indicates this information can be provided in a timely manner for incorporation into clinical practice. Profiling results will enable: 1) selection of pts with appropriate tumor targets for investigational targeted agents, 2) enhanced study enrollment, 3) evaluation of FDA approved targeted agents in off-label tumor types, and 4) correlation of treatment outcomes with patterns of tumor molecular abnormalities. [Table: see text]

scholarly journals Ethics of Mandatory Research Biopsy for Correlative End Points Within Clinical Trials in Oncology

2010 ◽  
Vol 28 (15) ◽  
pp. 2635-2640 ◽  
Author(s):  
Jeffrey Peppercorn ◽  
Iuliana Shapira ◽  
Deborah Collyar ◽  
Teresa Deshields ◽  
Nancy Lin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Decision Making ◽  
Predictive Biomarkers ◽  
Clinical Decision ◽  
Cancer Tissue ◽  
End Points ◽  
Research Participants ◽  
Group B ◽  
Treatment Alternatives

Clinical investigators in oncology are increasingly interested in using molecular analysis of cancer tissue to understand the biologic bases of response or resistance to novel interventions and to develop prognostic and predictive biomarkers that will guide clinical decision making. Some scientific questions of this nature can only be addressed, or may best be addressed, through the conduct of a clinical trial in which research biopsies are obtained from all participants. However, trial designs with mandatory research biopsies have raised ethical concerns related to the risk of harm to participants, the adequacy of voluntary informed consent, and the potential for misunderstanding among research participants when access to an experimental intervention is linked to the requirement to undergo a research biopsy. In consideration of the ethical and scientific issues at stake in this debate, the Cancer and Leukemia Group B Ethics Committee proposes guidelines for clinical trials involving mandatory research biopsies. Any cancer clinical trial that requires research biopsies of participants must be well designed to address the scientific question, obtain the biopsy in a way that minimizes risk, and ensure that research participants are fully informed of the risks, rationale, and requirements of the study, as well as of treatment alternatives. Further guidelines and discussions of this issue are specified in this position paper. We feel that if these principles are respected, an informed adult with cancer can both understand and voluntarily consent to participation in a clinical trial involving mandatory research biopsy for scientific end points.

scholarly journals A New Device to Automate the Monitoring of Critical Patients’ Urine Output

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Abraham Otero ◽  
Andrey Apalkov ◽  
Roemi Fernández ◽  
Manuel Armada
Keyword(s):  
Patient Outcomes ◽  
Urine Output ◽  
Clinical Decision Making ◽  
Capacitive Sensor ◽  
Clinical Decision ◽  
In Vitro Tests ◽  
Therapeutic Goals ◽  
New Device ◽  
Improve Patient

Urine output (UO) is usually measured manually each hour in acutely ill patients. This task consumes a substantial amount of time. Furthermore, in the literature there is evidence that more frequent (minute-by-minute) UO measurement could impact clinical decision making and improve patient outcomes. However, it is not feasible to manually take minute-by-minute UO measurements. A device capable of automatically monitoring UO could save precious time of the healthcare staff and improve patient outcomes through a more precise and continuous monitoring of this parameter. This paper presents a device capable of automatically monitoring UO. It provides minute by minute measures and it can generate alarms that warn of deviations from therapeutic goals. It uses a capacitive sensor for the measurement of the UO collected within a rigid container. When the container is full, it automatically empties without requiring any internal or external power supply or any intervention by the nursing staff. In vitro tests have been conducted to verify the proper operation and accuracy in the measures of the device. These tests confirm the viability of the device to automate the monitoring of UO.

scholarly journals Communication of Pharmacogenomic Test Results and Treatment Plans in Pediatric Oncology: Deliberative Stakeholder Consultations with Parents

2020 ◽  
Author(s):  
Cristina Longo ◽  
Vasiliki Rahimzadeh ◽  
Gillian Bartlett
Keyword(s):  
Small Group ◽  
Brain Cancer ◽  
Clinical Decision Making ◽  
Treatment Options ◽  
Effective Communication ◽  
Clinical Decision ◽  
Current Treatment ◽  
Communication Strategy ◽  
Communication Preferences ◽  
Care Experience

Abstract Background: Effective communication in support of clinical decision-making is central to the pediatric cancer care experience for families. A new laboratory derived pharmacogenetic test (LDT) that can diagnose difficult-to-treat brain cancers has been developed to stratify children based on their ability to respond to available treatment; however, the potential implementation of the LDT may make effective communication challenging since it can potentially remove the option for curative treatment in those children identified as non-responders, i.e. those with a catastrophic diagnosis. Objective: We solicited the perspectives of parents of children with difficult-to-treat brain cancer on communication preferences surrounding the potential implementation of the LDT in standard care using deliberative stakeholder consultations.Methods: Eight bereaved parents of children who succumbed to difficult-to-treat brain cancer, and four parents of children currently undergoing treatment for similar cancers attended separate small-group deliberative consultations – a stakeholder engagement method that enables the co-creation of recommendations following the consideration of competing arguments and diverse opinions of parents with different experiences. In the small-group consultations (Phase I), parents discussed four questions about potential communication issues that may arise with the LDT in practice. In Phase II, a total of five parents from both stakeholder groups (4 bereaved and 1 in current treatment) attended a consultation, known as the ‘mixed’ consultation, with the purpose of co-developing concrete recommendations for implementation of the LDT.Results: Explaining the risks, benefits, and accuracy of the LDT were considered essential to parents. Once an LDT-based diagnosis/prognosis can be made, parents valued honesty, empathy, and clarity in communication. Parents also requested that all results and treatment options be presented to them in measured doses, and in an unbiased manner over the course of several meetings. This communication strategy allowed sufficient time to understand and accept the diagnosis/prognosis, particularly if it was catastrophic. Continuous access to the appropriate psychological and social support or counselling at and post-diagnosis was also strongly recommended.Conclusions: Deliberants co-created family-centered recommendations surrounding communication issues of the LDT, providing guidance to pediatric oncologists that could implement the test in practice.

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