Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study.

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.

Patient-reported outcome measures and patient engagement in heart failure clinical trials: multi-stakeholder perspectives.

There are many consequences of heart failure (HF), including symptoms, impaired health-related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient-reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This 'minimal clinically important difference' requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed.

Views of Adolescents and Young Adults with Cancer and Their Oncologists Toward Patients' Participation in Genomic Research.

Purpose: With increased use of genomic testing in cancer research and clinical care, it is important to understand the perspectives and decision-making preferences of adolescents and young adults (AYAs) with cancer and their treating oncologists. Methods: We conducted an interview substudy of the BASIC3 Study, which enrolled newly diagnosed cancer patients <18 years of age with assent. Of 32 young adults (YAs) with cancer who reached the age of majority (AOM; 18 years) while on study, 12 were successfully approached and all consented to study continuation at AOM. Of those, seven completed an interview. Patients' oncologists, who enrolled and participated in return of clinical genomic results, were also interviewed (n = 12). Interviews were transcribed, deidentified, and analyzed using thematic analysis. Results: YAs cited the possibility of helping others and advancing science as major reasons for their assent to initial study enrollment and their willingness to consent at AOM. YAs thought obtaining informed consent from research participants for study continuation at AOM was a good idea in case they changed their minds or wanted to make their own decisions, and to keep them aware of study activities. There was diversity in what YAs understood and learned from genomic testing: some recalled specific findings, while some remembered minimal information about their results. Oncologists varied in their assessment of adolescents' engagement with the study and understanding of their results. Conclusion: Given the different ways AYAs engage with genomic information, careful assessment of AYAs' diverse communication and decision-making preferences is needed to tailor interactions accordingly.

Patient-reported Experience of Diagnosis, Management, and Burden of Renal Cell Carcinomas: Results from a Global Patient Survey in 43 Countries.

The International Kidney Cancer Coalition (IKCC) is a federation of 46 affiliated patient organisations representing 1.2 million patients worldwide that is committed to reducing the global burden of kidney cancer. A large-scale global survey of patients with renal cell carcinoma (RCC) to capture real-world experiences has never been undertaken. The 35-question survey was designed to identify geographic variations in patient education, experience, awareness, access to care, best practices, quality of life, and unmet psychosocial needs. A total of 1983 responses were recorded from 43 countries in 14 languages. Analysis revealed key findings. (1) At diagnosis, 43% of all respondents had no understanding of their RCC subtype. (2) Shared decision-making remains aspirational: globally, 29% of all patients reported no involvement in their treatment decision, responding "My doctor decided for me". (3) While 96% of respondents reported psychosocial impacts, surprisingly, only 50% disclosed them to their health care team. (4) Lastly, 70% of patients were not asked to participate in a clinical trial, although 90% indicated they would be interested. The survey reflects patient perspectives from diverse clinical scenarios in which different treatment options are available. The data point to actionable deficits in the fields of clinical trials, psychosocial support, and shared decision-making. PATIENT SUMMARY: In this brief report, we highlight the key results from the first large-scale global survey of patients with kidney cancer to capture real-world experiences. This survey reflects patient perspectives from diverse clinical scenarios in which different treatment options are available. We conclude that there is a need for improvement in the fields of clinical trials, psychosocial support, and shared decision-making.

Patient partnership in cardiovascular clinical trials.

Patients are ultimately the end-users of medical therapies and need to be actively integrated as contributors and decision-makers in the process of product development throughout product lifecycles. This is increasingly being recognized by patients, investigators, regulators, payers, sponsors, and medical journals. However, cardiovascular research remains behind other fields in terms of the extent of patient involvement and awareness of clinical trials in cardiovascular research. True patient partnerships in cardiovascular therapeutic development may permit more rapid recognition of unmet needs, ensure alignment of product development priorities with patient priorities, improve efficiency of trials (e.g. recruitment), and ensure outcomes of value to patients are being measured in trials (e.g. quality of life). This paper reviews ongoing initiatives and remaining opportunities to accomplish contributive patient involvement in cardiovascular clinical research.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle.

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care.