Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells.

2021

2021 Jan 25

1759-4782

<p>As clinical advances with chimeric antigen receptor (CAR) T cells are increasingly described and the potential for extending their therapeutic benefit grows, optimizing the implementation of this therapeutic modality is imperative. The recognition and management of cytokine release syndrome (CRS) marked a milestone in this field; however, beyond the understanding gained in treating CRS, a host of additional toxicities and/or potential late effects of CAR T cell therapy warrant further investigation. A multicentre initiative involving experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation was convened to facilitate the comprehensive study of extended CAR&nbsp;T cell-mediated toxicities and establish a framework for new systematic investigations of CAR T cell-related adverse events. Together, this group identified six key focus areas: extended monitoring of neurotoxicity and neurocognitive function, psychosocial considerations, infection and immune reconstitution, other end organ toxicities, evaluation of subsequent neoplasms, and strategies to optimize remission durability. Herein, we present the current understanding, gaps in knowledge and future directions of research addressing these CAR T cell-related outcomes. This systematic framework to study extended toxicities and optimization strategies will facilitate the translation of acquired experience and knowledge for optimal application of CAR T cell therapies.</p>

10.1038/s41571-020-00456-y

Nat Rev Clin Oncol

33495553

Challenges and Priorities for Pediatric Palliative Care Research in the United States and Similar Practice Settings: Report from a Pediatric Palliative Care Research Network Workshop.

2019

2019 Aug 21

1873-6513

<p><strong>CONTEXT: </strong>In order to dramatically advance the evidence base for pediatric palliative care (PPC) interventions, practices, and programs in the United States and similar practice settings, the field needs to better understand the challenges and opportunities for rigorous scholarship.</p>

<p><strong>OBJECTIVES: </strong>The Pediatric Palliative Care Research Network conducted a workshop to clarify challenges and identify key priorities.</p>

<p><strong>METHODS: </strong>The workshop focused on PPC research topics and methods, including: outcomes measurement, qualitative inquiry, analyses of "big data," prospective collection of research data, case series and cohort studies, and intervention trials, with synthesizing summary and follow-up discussions. All attendees reviewed and approved the final report.</p>

<p><strong>RESULTS: </strong>Five common challenges were identified: patient diversity and small population size; interdependencies and dynamic interactions between child, family members, and disease processes over time; outcomes and measurement; workforce and infrastructure limitations; and presumed burden of PPC research upon participants. Seven priorities emerged: bolster training and development of PPC investigators; develop core resources; advance symptom measurement (and measurements of other exposures and outcomes); improve symptom management and quality of life interventions; improve communication, elicitation of goals of care, and decision-making; understand family impact and facilitate or improve family adaptation and coping; and analyze and improve systems of care, policy, and education.</p>

<p><strong>CONCLUSION: </strong>These challenges and priorities identify key research areas that can guide individual investigators and research funders to advance the field.</p>

10.1016/j.jpainsymman.2019.08.011

J Pain Symptom Manage

31445136

Ethics, Emotions, and the Skills of Talking About Progressing Disease With Terminally Ill Adolescents: A Review.

2016

1216-23

2016 Dec

2168-6211

<p><strong>Importance: </strong>For clinicians caring for adolescent patients living with progressive, life-threatening illness, discussions regarding prognosis, goals of care, and treatment options can be extremely challenging. While clinicians should respect and help to facilitate adolescents' emerging autonomy, they often must also work with parents' wishes to protect patients from the emotional distress of hearing bad news.</p>

<p><strong>Observations: </strong>We reviewed the ethical justifications for and against truth-telling, and we considered the published ethical and practice guidance, as well as the perspectives of patients, parents, and clinicians involved in these cases. We also explored particular challenges with respect to the cultural context, timing, and content of conversations at the end of adolescents' lives. In most cases, clinicians should gently but persistently engage adolescents directly in conversations about their disease prognosis and corresponding hopes, worries, and goals. These conversations need to occur multiple times, allowing significant time in each discussion for exploration of patient and family values. While truth-telling does not cause the types of harm that parents and clinicians may fear, discussing this kind of difficult news is almost always emotionally distressing. We suggest some "phrases that help" when clinicians strive to deepen understanding and facilitate difficult conversations with adolescents, parents, and other family members.</p>

<p><strong>Conclusions and Relevance: </strong>The pediatrician's opportunities to engage in difficult conversations about poor prognosis may be rare, but such conversations can be crucial. These discussions affect how patients live at the end of their lives, how they die, and how their families go on. Improved understanding of basic principles of communication, as well as augmented understanding of patient, family, and clinician perspectives may better enable us to navigate these important conversations.</p>

10.1001/jamapediatrics.2016.2142

JAMA Pediatr

27749945

Advancing a comprehensive cancer care agenda for children and their families: Institute of Medicine Workshop highlights and next steps.

2016

2016 May 4

1542-4863

<p>This article highlights key findings from the "Comprehensive Cancer Care for Children and Their Families" March 2015 joint workshop by the Institute of Medicine (IOM) and the American Cancer Society. This initiative convened more than 100 family members, clinician investigators, advocates, and members of the public to discuss emerging evidence and care models and to determine the next steps for optimizing quality-of-life outcomes and well-being for children and families during pediatric cancer treatment, after treatment completion, and across the life spectrum. Participants affirmed the triple aim of pediatric oncology that strives for every child with cancer to be cured; provides high-quality palliative and psychosocial supportive, restorative, and rehabilitative care to children and families throughout the illness course and survivorship; and assures receipt of high-quality end-of-life care for patients with advancing disease. Workshop outcomes emphasized the need for new pediatric cancer drug development and identified critical opportunities to prioritize palliative care and psychosocial support as an integral part of pediatric cancer research and treatment, including the necessity for adequately resourcing these supportive services to minimize suffering and distress, effectively address quality-of-life needs for children and families at all stages of illness, and mitigate the long-term health risks associated with childhood cancer and its treatment. Next steps include dismantling existing silos and enhancing collaboration between clinical investigators, disease-directed specialists, and supportive care services; expanding the use of patient-reported and parent-reported outcomes; effectively integrating palliative and psychosocial care; and clinical communication skills development. CA Cancer J Clin 2016. © 2016 American Cancer Society.</p>

10.3322/caac.21347

CA Cancer J Clin

27145249

International and Interdisciplinary Identification of Health Care Transition Outcomes.

2016

205-11

2016 Mar 1

2168-6211

<p><strong>IMPORTANCE: </strong>There is a lack of agreement on what constitutes successful outcomes for the process of health care transition (HCT) among adolescent and young adults with special health care needs.</p>

<p><strong>OBJECTIVE: </strong>To present HCT outcomes identified by a Delphi process with an interdisciplinary group of participants.</p>

<p><strong>DESIGN, SETTING, AND PARTICIPANTS: </strong>A Delphi method involving 3 stages was deployed to refine a list of HCT outcomes. This 18-month study (from January 5, 2013, of stage 1 to July 3, 2014, of stage 3) included an initial literature search, expert interviews, and then 2 waves of a web-based survey. On this survey, 93 participants from outpatient, community-based, and primary care clinics rated the importance of the top HCT outcomes identified by the Delphi process. Analyses were performed from July 5, 2014, to December 5, 2014.</p>

<p><strong>EXPOSURES: </strong>Health care transition outcomes of adolescents and young adults with special health care needs.</p>

<p><strong>MAIN OUTCOMES AND MEASURES: </strong>Importance ratings of identified HCT outcomes rated on a Likert scale from 1 (not important) to 9 (very important).</p>

<p><strong>RESULTS: </strong>The 2 waves of surveys included 117 and 93 participants as the list of outcomes was refined. Transition outcomes were refined by the 3 waves of the Delphi process, with quality of life being the highest-rated outcome with broad agreement. The 10 final outcomes identified included individual outcomes (quality of life, understanding the characteristics of conditions and complications, knowledge of medication, self-management, adherence to medication, and understanding health insurance), health services outcomes (attending medical appointments, having a medical home, and avoidance of unnecessary hospitalization), and a social outcome (having a social network). Participants indicated that different outcomes were likely needed for individuals with cognitive disabilities.</p>

<p><strong>CONCLUSIONS AND RELEVANCE: </strong>Quality of life is an important construct relevant to HCT. Future research should identify valid measures associated with each outcome and further explore the role that quality of life plays in the HCT process. Achieving consensus is a critical step toward the development of reliable and objective comparisons of HCT outcomes across clinical conditions and care delivery locations.</p>

10.1001/jamapediatrics.2015.3168

JAMA Pediatr

26619178