Electroacupuncture for the management of symptom clusters in cancer patients and survivors (EAST).

BACKGROUND: Neuropsychiatric symptoms, comprising cognitive impairment, fatigue, insomnia, depression, and anxiety, are prevalent and may co-occur during and after chemotherapy treatment for cancer. Electroacupuncture (EA), which involves mild electrical stimulation with acupuncture, holds great potential in addressing the management of individual symptoms. However, there is a lack of studies evaluating if EA can manage concurrent neuropsychiatric symptoms in cancer (i.e., symptom cluster). Hence, we designed a trial to evaluate the efficacy, safety, and feasibility of administering EA as an intervention to mitigate neuropsychiatric symptom clusters amongst cancer patients and survivors. METHODS: The EAST study is a randomized, sham-controlled, patient- and assessor-blinded clinical trial. Sixty-four cancer patients and survivors with complaints of one or more neuropsychiatric symptom(s) in the seven days prior to enrollment are recruited from the University of California Irvine (UCI) and Children's Hospital of Orange County (CHOC). Individuals with needle phobia, metastases, bleeding disorders, electronic implants, epilepsy, exposure to acupuncture in the three months prior to enrollment, and who are breastfeeding, pregnant, or planning to get pregnant during the duration of the study will be excluded. Screening for metal fragments and claustrophobia are performed prior to the optional neuroimaging procedures. Recruited patients will be randomized (1:1) in random blocks of four or six to receive either ten weekly verum EA (treatment arm, vEA) or weekly sham EA (control arm, sEA) treatment visits with a follow-up appointment four to twelve weeks after their last treatment visit. The treatment arm will receive EA at 13 acupuncture points (acupoints) chosen for their therapeutic effects, while the control arm receives minimal EA at 7 non-disease-related acupoints. Questionnaires and cognitive assessments are administered, and blood drawn to assess changes in symptom clusters and biomarkers, respectively. CONCLUSION: The EAST study can provide insight into the efficacy of EA, an integrative medicine modality, in the management of cancer symptom clusters in routine clinical practice. TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT05283577.

Voicing their choices: Advance care planning with adolescents and young adults with cancer and other serious conditions.

OBJECTIVES: To determine whether engaging in advance care planning (ACP) using a formal tool, Voicing My CHOiCES (VMC), would alleviate adolescent and young adults (AYAs) anxiety surrounding ACP and increase social support and communication about end-of-life care preferences with family members and health care providers (HCPs). METHODS: A total of 149 AYAs aged 18-39 years receiving cancer-directed therapy or treatment for another chronic medical illness were enrolled at seven US sites. Baseline data included prior ACP communication with family members and HCPs and measures of generalized anxiety, ACP anxiety, and social support. Participants critically reviewed each page of VMC and then completed three pages of the document. ACP anxiety was measured again immediately after the completion of VMC pages. One month later, participants repeated anxiety and social support measures and were asked if they shared what they had completed in VMC with a family member or HCP. RESULTS: At baseline, 50.3% of participants reported that they previously had a conversation about EoL preferences with a family member; 19.5% with an HCP. One month later, 65.1% had subsequently shared what they wrote in VMC with a family member; 8.9% shared with an HCP. Most (88.6%) reported they would not have had this conversation if not participating in the study. No significant changes occurred in social support. There was an immediate drop in anxiety about EoL planning after reviewing VMC which persisted at 1 month. Generalized anxiety was also significantly lower 1 month after reviewing VMC. SIGNIFICANCE OF RESULTS: Having a document specifically created for AYAs to guide ACP planning can decrease anxiety and increase communication with family members but not necessarily with HCPs. Future research should examine ways ACP can be introduced more consistently to this young population to allow their preferences for care to be heard, respected, and honored, particularly by their healthcare providers.

Adolescent and Young Adult Initiated Discussions of Advance Care Planning: Family Member, Friend and Health Care Provider Perspectives.

Background and Aims: End-of-life (EoL) discussions can be difficult for seriously ill adolescents and young adults (AYAs). Researchers aimed to determine whether completing Voicing My CHOiCES (VMC)-a research-informed advance care planning (ACP) guide-increased communication with family, friends, or health care providers (HCPs), and to evaluate the experience of those with whom VMC was shared. Methods: Family, friends, or HCPs who the AYAs had shared their completed VMC with were administered structured interviews to assess their perception of the ACP discussion, changes in their relationship, conversation quality, and whether the discussion prompted changes in care. Open-ended responses underwent thematic analysis. Results: One-month post-completion, 65.1% of AYA had shared VMC completion with a family member, 22.6% with a friend, and 8.9% with an HCP. Among a sample of respondents, family (47%) and friends (33%) reported a positive change in their relationship with the AYA. Participant descriptions of the experience fell into five themes: positive experience (47%), difficult experience (44%), appreciated a guide to facilitate discussion (35%), provided relief (21%), and created worry/anxiety (9%). Only 1 HCP noted a treatment change. Family (76%), friends (67%), and HCP (50%) did not think the AYA would have discussed EoL preferences without completing VMC. Conclusions: VMC has potential to enhance communication about ACP between AYA and their family and friends, though less frequently with HCPs. Participants reported a positive change in their relationship with the AYA after discussing VMC, and described experiencing the conversation as favorable, even when also emotionally difficult.

Southern California Pediatric and Adolescent Cancer Survivorship (SC-PACS): Establishing a Multi-Institutional Childhood, Adolescent, and Young Adult Cancer Survivorship Consortium in Southern California.

Introduction Given their risk for late effects and early mortality, childhood/adolescent cancer survivors (CACSs) should receive longitudinal monitoring and care. The Southern California Pediatric and Adolescent Cancer Survivorship (SC-PACS) consortium was established in February 2017 to combine resources and expertise across seven participating survivorship programs. Its over-arching objective is to address the unique needs of its demographically diverse CACS population through collaborative survivorship research and care initiatives. The first SC-PACS study was an assessment of survivorship needs and evaluation of current services as reported by CACSs and their parents/primary care givers (PPCGs) receiving survivorship care at consortium sites. Methods As an initial investigation, a cross-sectional survey for CACSs and their parents/primary care givers was conducted. The goal was to enroll 10 CACSs and 10 PPCGs from each of the seven institutions (total of 140 participants). The eligibility criteria for CACSs were age ≥13 years at the time of enrollment, >2 years from the end of treatment, sufficient cognitive function to complete the survey, and English or Spanish language proficiency. For CACSs <13 years old, their PPCGs completed the survey. This was a convenience sample using frequencies and proportions to describe participant characteristics and survey responses, which were entered into a Research Electronic Data Capture (REDCap) database. Results Across the consortium, of the recruitment target of 140 participants (CACSs, n=70; PPCGs, n=70), 127 (90.7%) participants were enrolled. Of the 127 participants enrolled, 65 (51.2%) were CACSs and 62 (48.8%) were PPCGs. The majority of participants were female (51.2%), were Hispanic (62.2%), spoke English as the primary language at home (57.5%), and were diagnosed between one to four years of age (45.7%). Information considered most important by both CACSs and PPCGs was related to cancer diagnosis (90.8%) and future risks as a result of cancer treatment received (98.0%). Overall, 78% of CACSs and PPCGs found the survivorship information (treatment summary) useful, and 83% felt that they received the right amount of information about their cancer. Conclusion Our aim was to obtain baseline data that would characterize our CACS population, inform consortium priorities, and establish a collaborative research platform. The ultimate goal of the consortium is to develop a comprehensive survivorship care approach that addresses the most important needs of cancer survivors in our catchment area and promotes best practice interventions. Future plans are to expand the needs assessment survey to obtain a wider representation of the survivor population at SC-PACS institutions, helping create strategies to improve cancer-specific education, delivery of treatment summary, and access to community resources for this demographically and socioeconomically diverse population.

Persistent Gut Microbial Dysbiosis in Children with Acute Lymphoblastic Leukemia (ALL) During Chemotherapy.

Prophylactic or therapeutic antibiotic use along with chemotherapy treatment potentially has a long-standing adverse effect on the resident gut microbiota. We have established a case-control cohort of 32 pediatric and adolescent acute lymphoblastic leukemia (ALL) patients and 25 healthy siblings (sibling controls) to assess the effect of chemotherapy as well as antibiotic prophylaxis on the gut microbiota. We observe that the microbiota diversity and richness of the ALL group is significantly lower than that of the control group at diagnosis and during chemotherapy. The microbiota diversity is even lower in antibiotics-exposed ALL patients. Although the gut microbial diversity tends to stabilize after 1-year post-chemotherapy, their abundances were altered because of chemotherapy and prophylactic antibiotic treatments. Specifically, the abundances of mucolytic gram-positive anaerobic bacteria, including Ruminococcus gnavus and Ruminococcus torques, tended to increase during the chemotherapy regimen and continued to be elevated 1 year beyond the initiation of chemotherapy. This dysbiosis may contribute to the development of gastrointestinal complications in ALL children following chemotherapy. These findings set the stage to further understand the role of the gut microbiome dynamics in ALL patients and their potential role in alleviating some of the adverse side effects of chemotherapy and antibiotics use in immunocompromised children.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes. Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer. Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017. Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners. Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information. Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%). Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

A tale of four practices.

Purpose The Patient-Centered Medical Home (PCMH) has become a dominant model of primary care re-design. This transformation presents a challenge to many care delivery organizations. The purpose of this paper is to describe attributes shaping successful and unsuccessful practice transformation within four medical practice groups. Design/methodology/approach As part of a larger study of 25 practices transitioning into a PCMH, the current study focused on diabetes care and identified high- and low-improvement medical practices in terms of quantitative patient measures of glycosylated hemoglobin and qualitative assessments of practice performance. A subset of the top two high-improvement and bottom two low-improvement practices were identified as comparison groups. Semi-structured interviews were conducted with diverse personnel at these practices to investigate their experiences with practice transformation and data were analyzed using analytic induction. Findings Results show a variety of key attributes facilitating more successful PCMH transformation, such as empanelment, shared goals and regular meetings, and a clear understanding of PCMH transformation purposes, goals, and benefits, providing care/case management services, and facilitating patient reminders. Several barriers also exist to successful transformation, such as low levels of resources to handle financial expense, lack of understanding PCMH transformation purposes, goals, and benefits, inadequate training and management of technology, and low team cohesion. Originality/value Few studies qualitatively compare and contrast high and low performing practices to illuminate the experience of practice transformation. These findings highlight the experience of organizational members and their challenges in practice transformation while providing quality diabetes care.

Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis.

BACKGROUND: An estimated 15,000 children and adolescents under the age of 19 years are diagnosed with leukemia, lymphoma and other tumors in the USA every year. All children and adolescent acute leukemia patients will undergo chemotherapy as part of their treatment regimen. Fortunately, survival rates for most pediatric cancers have improved at a remarkable pace over the past three decades, and the overall survival rate is greater than 90 % today. However, significant differences in survival rate have been found in different age groups (94 % in 1-9.99 years, 82 % in ≥10 years and 76 % in ≥15 years). ALL accounts for about three out of four cases of childhood leukemia. Intensive chemotherapy treatment coupled with prophylactic or therapeutic antibiotic use could potentially have a long-term effect on the resident gastrointestinal (GI) microbiome. The composition of GI microbiome and its changes upon chemotherapy in pediatric and adolescent leukemia patients is poorly understood. In this study, using 16S rRNA marker gene sequences we profile the GI microbial communities of pediatric and adolescent acute leukemia patients before and after chemotherapy treatment and compare with the microbiota of their healthy siblings. RESULTS: Our study cohort consisted of 51 participants, made up of matched pediatric and adolescent patients with ALL and a healthy sibling. We elucidated and compared the GI microbiota profiles of patients and their healthy sibling controls via analysis of 16S rRNA gene sequencing data. We assessed the GI microbiota composition in pediatric and adolescent patients with ALL during the course of chemotherapy by comparing stool samples taken before chemotherapy with stool samples collected at varying time points during the chemotherapeutic treatment. The microbiota profiles of both patients and control sibling groups are dominated by members of Bacteroides, Prevotella, and Faecalibacterium. At the genus level, both groups share many taxa in common, but the microbiota diversity of the patient group is significantly lower than that of the control group. It was possible to distinguish between the patient and control groups based on their microbiota profiles. The top taxa include Anaerostipes, Coprococcus, Roseburia, and Ruminococcus2 with relatively higher abundance in the control group. The observed microbiota changes are likely the result of several factors including a direct influence of therapeutic compounds on the gut flora and an indirect effect of chemotherapy on the immune system, which, in turn, affects the microbiota. CONCLUSIONS: This study provides significant information on GI microbiota populations in immunocompromised children and opens up the potential for developing novel diagnostics based on stool tests and therapies to improve the dysbiotic condition of the microbiota at the time of diagnosis and in the earliest stages of chemotherapy.

Molecular Genetic Profiling of Adolescent Glassy Cell Carcinoma of the Cervix Reveals Targetable EGFR Amplification with Potential Therapeutic Implications.

Glassy cell carcinoma of the cervix (GCCC) is a very rare and aggressive form of cervical cancer. An adolescent female with advanced metastatic disease was enrolled in our genomic profiling research protocol. We identified high-level amplification of epidermal growth factor receptor (EGFR) and Yes-associated protein-1 (YAP1), which led to the addition of EGFR inhibitors to the chemotherapy regimen. Here, we report the first genetically profiled case of GCCC with potential therapeutic implications.

Successful Treatment of Genetically Profiled Pediatric Extranodal NK/T-Cell Lymphoma Targeting Oncogenic STAT3 Mutation.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is a distinct type of non-Hodgkin lymphoma predominantly observed in Asian and Latin American adult males. A 12-year-old Hispanic female diagnosed with ENKTCL was enrolled in our genomic profiling research protocol. We identified specific somatic alterations consistent with diagnosis of ENKTCL as well as oncogenic mutations in MAP2K1 and STAT3. To our knowledge, this is the first report of an immunophenotypically confirmed and genetically profiled case of ENKTCL in a female pediatric patient in the United States, including its unique treatment and favorable outcome.

Adolescent and young adult patients with cancer: a milieu of unique features.

Adolescent and young adult (AYA) patients with cancer are a unique category of patients who, depending on age at time of diagnosis, might receive treatment from oncologists specializing either in the treatment of children or adults. In the USA, AYA oncology generally encompasses patients 15-39 years of age. AYA patients with cancer typically present with diseases that span the spectrum from 'paediatric' cancers (such as acute lymphoblastic leukaemia [ALL] and brain tumours) to 'adult' tumours (such as breast cancer and melanoma), as well as cancers that are largely unique to their age group (such as testicular cancer and bone tumours). Research indicates that outcomes of AYA patients with cancer are influenced not only by the treatment provided, but also by factors related to 'host' biology. In addition to the potential biological and cancer-specific differences between AYAs and other patients with cancer, AYA patients also often have disparate access to clinical trials and suffer from a lack of age-appropriate psychosocial support services and health services, which might influence survival as well as overall quality of life. In this Review, these issues are discussed, with a focus on two types of AYA cancer--ALL and melanoma--highlighting findings arising from the use of emerging technologies, such as whole-genome sequencing.