Dataset Information

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making.

ABSTRACT: Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R (clinicaltrials.gov identifier 00001337).

SUBMITTER: Melani C

PROVIDER: S-EPMC6068044 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making.

Melani Christopher C Advani Ranjana R Roschewski Mark M Walters Kelsey M KM Chen Clara C CC Baratto Lucia L Ahlman Mark A MA Miljkovic Milos D MD Steinberg Seth M SM Lam Jessica J Shovlin Margaret M Dunleavy Kieron K Pittaluga Stefania S Jaffe Elaine S ES Wilson Wyndham H WH

Haematologica 20180510 8

Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPO ...[more]

PMID: 29748435

Similar Datasets

Project description:In a social group, animals make behavioral decisions that fit their social ranks. These behavioral choices are dependent on the various social cues experienced during social interactions. In vertebrates, little is known of how social status affects the underlying neural mechanisms regulating decision-making circuits that drive competing behaviors. Here, we demonstrate that social status in zebrafish (Danio rerio) influences behavioral decisions by shifting the balance in neural circuit activation between two competing networks (escape and swim). We show that socially dominant animals enhance activation of the swim circuit. Conversely, social subordinates display a decreased activation of the swim circuit, but an enhanced activation of the escape circuit. In an effort to understand how social status mediates these effects, we constructed a neurocomputational model of the escape and swim circuits. The model replicates our findings and suggests that social status-related shift in circuit dynamics could be mediated by changes in the relative excitability of the escape and swim networks. Together, our results reveal that changes in the excitabilities of the Mauthner command neuron for escape and the inhibitory interneurons that regulate swimming provide a cellular mechanism for the nervous system to adapt to changes in social conditions by permitting the animal to select a socially appropriate behavioral response.SIGNIFICANCE STATEMENT Understanding how social factors influence nervous system function is of great importance. Using zebrafish as a model system, we demonstrate how social experience affects decision making to enable animals to produce socially appropriate behavior. Based on experimental evidence and computational modeling, we show that behavioral decisions reflect the interplay between competing neural circuits whose activation thresholds shift in accordance with social status. We demonstrate this through analysis of the behavior and neural circuit responses that drive escape and swim behaviors in fish. We show that socially subordinate animals favor escape over swimming, while socially dominants favor swimming over escape. We propose that these differences are mediated by shifts in relative circuit excitability.

Project description:Background:Multiple technologies, procedures and programs call for fairly-based decisions for prioritization of healthcare interventions. There is a diversity of perspectives of what constitutes a legitimate decision, which depends on both the process and the reasoning applied. Current approaches focus on technical aspects while methods to support alignment of decisions with the compassionate impetus of healthcare systems is lacking. Methods:The framework was developed based on an analysis of the foundations of healthcare systems, the reasoning underlying decisions and fair processes. The concept of reflective multicriteria was created: it assumes that decisionmakers guided by a generic interpretative frame rooted in the compassionate impetus of healthcare systems, can sharpen their reasoning, raise awareness of their motivation and increase legitimacy of decisions. The initial framework was made available through a not for profit organization (the EVIDEM Collaboration, 2006-2017) to stimulate its development with thought leaders and stakeholders in an open source philosophy. Development was tailored to the real-life needs of decisionmakers and drew on several domains of knowledge including healthcare ethics, evidenced-based medicine, health economics, health technology assessment and multicriteria approaches. Results:The 10th edition framework builds on four dimensions: (1) the universal impetus of healthcare systems, (2) reasoning, values and ethics, (3) evidence and knowledge on interventions, and (4) a transformative process. Mathematical aspects of the framework are designed to help clarify, express and share individual reasoning; this non-conventional use of numbers requires a cultural change and needs to be phased in slowly. The framework includes four tools for easy adaptation and operationalization: (a) concepts and operationalization, (b) adapt and pilot, (c) evidence matrix, (d) mathematical representation of reasoning. Application is useful throughout all types of healthcare interventions, for all levels of decision, and across the globe. Conclusion:By clarifying their reasoning while keeping decisionmakers aware of the impetus of healthcare systems, reflective multicriteria provides an effective approach to increase the legitimacy of decisions. Beyond a tool, reflective multicriteria pioneered by EVIDEM is geared to transform our vision of the value of healthcare interventions and how they might contribute to relevant, equitable and sustainable healthcare systems.

Project description:Little is known about what role physicians take in the decision-making process about life support in intensive care units.To determine how responsibility is balanced between physicians and surrogates for life support decisions and to empirically develop a framework to describe different models of physician involvement.Multi-centered study of audio-taped clinician-family conferences with a derivation and validation cohort.Intensive care units of four hospitals in Seattle, Washington, in 2000 to 2002 and two hospitals in San Francisco, California, in 2006 to 2008.Four hundred fourteen clinicians and 495 surrogates who were involved in 162 life support decisions.In the derivation cohort (n = 63 decisions), no clinician inquired about surrogates' preferred role in decision-making. Physicians took one of four distinct roles: 1) informative role (7 of 63) in which the physician provided information about the patient's medical condition, prognosis, and treatment options but did not elicit information about the patient's values, engage in deliberations, or provide a recommendation about whether to continue life support; 2) facilitative role (23 of 63), in which the physician refrained from providing a recommendation but actively guided the surrogate through a process of clarifying the patients' values and applying those values to the decision; 3) collaborative role (32 of 63), in which the physician shared in deliberations with the family and provided a recommendation; and 4) directive role (1 of 63), in which the physician assumed all responsibility for, and informed the family of, the decision. In 10 out of 20 conferences in which surrogates requested a recommendation, the physician refused to provide one. The validation cohort revealed a similar frequency of use of the four roles, and frequent refusal by physicians to provide treatment recommendations.There is considerable variability in the roles physicians take in decision-making about life support with surrogates but little negotiation of desired roles. We present an empirically derived framework that provides a more comprehensive view of physicians' possible roles.

Project description:This study investigates if and under which conditions humans are able to identify and follow the most advantageous leader who will them provide with the most resources. In an iterated economic game with the aim of earning monetary reward, 150 participants were asked to repeatedly choose one out of four leaders. Unbeknownst to participants, the leaders were computer-controlled and programmed to yield different expected payout values that participants had to infer from repeated interaction over 30 rounds. Additionally, participants were randomly assigned to one of three conditions: single, independent, or cohesion. The conditions were designed to investigate the ideal circumstances that lead to identifying the most advantageous leader: when participants are alone (single condition), in a group that lets individuals sample information about leaders independently (independent condition), or in a group that is rewarded for cohesive behavior (cohesion condition). Our results show that participants are generally able to identify the most advantageous leader. However, participants who were incentivized to act cohesively in a group were more likely to settle on a less advantageous leader. This suggests that cohesion might have a detrimental effect on group decision making. To test the validity of this finding, we explore possible explanations for this pattern, such as the length of exploration and exploitation phases, and present techniques to check for confounding factors in group experiments in order to identify or exclude them as alternative explanations. Finally, we show that the chosen reward structure of the game strongly affects the observed following behavior in the group and possibly occludes other effects. We conclude with a recommendation to carefully choose reward structures and evaluate possible alternative explanations in experimental group research that should further pursue the study of exploration/exploitation phases and the influence of group cohesion on group decision making as promising topics for further research.

Dataset Information

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making.

Publications

End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure