Inflammatory myofibroblastic tumor (IMT) is a genetically heterogenous tumor of the viscera and soft tissues, with multiple molecular features having been demonstrated in this tumor type. About 50% ...of cases harbor an anaplastic lymphoma kinase (ALK) gene rearrangement, and recent studies have described novel fusions involving the ROS1 and PDGFRβ genes in a subset of ALK-negative cases. However, the molecular features of the remaining subset of cases are not yet defined. We report a case of a large, highly aggressive IMT of the lung in a 17-year-old girl. This case was molecularly characterized through whole-genome and transcriptome sequencing. Subsequently, we investigated a cohort of 15 ALK-negative IMTs of various anatomic sites. All cases were screened using fluorescence in situ hybridization (FISH) for rearrangement of the ETV6 locus and with reverse transcription polymerase chain reaction (RT-PCR) for the ETV6-NTRK3 fusion transcript. Whole-genome and transcriptome sequencing revealed an ETV6-NTRK3 fusion transcript in our index case. This was confirmed by FISH studies for ETV6 gene rearrangement, as well as by RT-PCR. In addition, 2 additional cases in our cohort demonstrated ETV6 rearrangement by FISH. The presence of ETV6-NTRK3 fusion transcript was demonstrated by RT-PCR in one of these additional cases. In summary, we demonstrate the expression of the ETV6-NTRK3 fusion oncogene in a small subset of IMTs, lending further support to the role of oncogenic tyrosine kinases in the pathophysiology of this tumor type. Our data also further expand the growing spectrum of tumor types expressing the ETV6-NTRK3 fusion.
Adolescent and young adult (AYA, ages 15–39 years) oncology patients are an underserved population with specialized needs. AYA programs are absent from most Canadian centers. We identified a priority ...list and sequence for new programs to address. Program goals, priorities, and activities were developed through literature review, national consensus documents, and expert opinion. Health care providers (HCPs) involved in AYA cancer care, administrators, and patient and family representatives were engaged to co-develop program goals and activities. A modified Delphi technique was used through two iterations followed by an in-person meeting to prioritize program implementation. Consensus was defined as a mean score of less than 2.0 (not important) or 4.0 or greater (important). Items without consensus (scored between 2.0 and 3.99) were discussed at the in-person meeting. Sixty provincial stakeholders completed the Delphi survey across multiple disciplines. Twenty-seven stakeholders attended the in-person meeting. All goals were deemed important, except development of a research program. Patient implementation tasks ranked highest. Priority sequence of implementation was: patient care first, followed by HCP education; patient and family education; program sustainability plan; evaluation; research; then a model for multidisciplinary tumor board review. These represent key goals for new AYA oncology programs and a priority sequence of implementation.
Pain is one of the most common and distressing symptoms reported by adolescents with cancer. Despite advancements in pain assessment and management research, pain due to cancer and/or its treatments ...continues to be poorly managed. Our research group has developed a native iPhone application (app) called Pain Squad to tackle the problem of poorly managed pain in the adolescent with cancer group. The app functions as an electronic pain diary and is unique in its ability to collect data on pain intensity, duration, location, and the impact pain has on an adolescent's life (ie, relationships, school work, sleep, mood). It also evaluates medications and other physical and psychological pain management strategies used. Users are prompted twice daily at configurable times to complete 20 questions characterizing their pain and the app transmits results to a database for aggregate reporting through a Web interface. Each diary entry represents a pain case filed by an adolescent with cancer and a reward system (ie, moving up through law-enforcement team ranks, built-in videotaped acknowledgements from fictitious officers) encourages consistent use of the diary.
Our objective was to design, develop, and test the usability, feasibility, compliance, and satisfaction of a game-based smartphone pain assessment tool for adolescents with cancer.
We used both low- and high-fidelity qualitative usability testing with qualitative semi-structured, audio-taped interviews and iterative cycles to design and refine the iPhone based Pain Squad app. Qualitative thematic analysis of interviews using constant comparative methodology captured emergent themes related to app usability. Content validity was assessed using question importance-rating surveys completed by participants. Compliance and satisfaction data were collected following a 2-week feasibility trial where users were alarmed to record their pain twice daily on the app.
Thematic analysis of usability interviews showed the app to be appealing overall to adolescents. Analyses of both low- and high-fidelity testing resulted in minor revisions to the app to refine the theme and improve its usability. Adolescents resoundingly endorsed the game-based nature of the app and its virtual reward system. The importance of app pain diary questions was established by content validity analysis. Compliance with the app, assessed during feasibility testing, was high (mean 81%, SD 22%) and adolescents from this phase of the study found the app likeable, easy to use, and not bothersome to complete.
A multifaceted usability approach demonstrated how the Pain Squad app could be made more appealing to children and adolescents with cancer. The game-based nature and built-in reward system of the app was appealing to adolescents and may have resulted in the high compliance rates and satisfaction ratings observed during clinical feasibility testing.
Abstract Purpose A biobank is defined as “a facility for the collection, preservation, storage and supply of biological samples and associated data, which follows standardized operating procedures ...and provides material for scientific and clinical use.” The practice of biobanking must consider the best interests of participants, which is especially complicated in the pediatric setting, where parents or guardians are responsible for consent of their children. Age of participant assent, consent, and reconsent at the age of majority are some of the issues which need to be addressed. Methods We conducted an exploratory survey of four cohorts: (1) adolescents aged 14–18 years treated at British Columbia Children's Hospital, Vancouver, British Columbia, Canada, in the Division of Oncology, Cardiology, or Orthopedics. (2) Parents of the adolescents described in (1). (3) Adolescents aged 14–18 years from high schools in Vancouver, British Columbia, Canada. (4) Parents of the adolescents described in (3). Results We show that clinic participants rated a higher willingness to donate specimens versus school participants. Furthermore, clinic participants felt assent was more important and parental consent alone was insufficient. The median suggested age for assent was 14.5 years among adolescent responses and 16 years from parental responses of both groups. School parents were the most conservative in their responses toward their child's participation in a biobank. Conclusions Adolescents, who were seen in clinics and their parents, had a more altruistic approach toward pediatric biobanking than those surveyed in the school setting. Additionally, parents are less comfortable making decisions regarding biobanking than their adolescent children.
Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and ...factors associated with enrollment on trials.
In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0-14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis.
There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001).
In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials.
The purpose of this study was to explore the attitudes of genomics researchers in a pediatric setting in the context of regulatory guidance recommending the disclosure of clinically significant ...research findings.
A validated 32-item questionnaire was sent to 107 researchers with two large-scale projects (the Canadian Pediatric Cancer Genome Consortium and the Finding of Rare Genes Canada Consortium). We examined researchers' attitudes toward obligations to offer genomic research results (including if the participant was deceased, a relative, or a child), influence of the certainty/severity of the condition on this obligation, and personal experiences.
Of the 107 researchers, 74 (69%) responded. Researchers did not feel a strong responsibility to look for meaningful incidental results in the research genomic data set (n = 27, 37%). However, once identified, they felt participants had a strong right to receive them, irrespective of being incidental (n = 50, 68%) or primary targets (n = 64, 87%). There was a high degree of support for informing siblings of genomic results (n = 46, 62%), especially for treatable conditions (n = 56, 76%). Less than half of the participants indicated that their research ethics board required an offer of results (n = 34, 46%) or provided a detailed process (n = 16, 22%).
Researchers strongly support the offer of targeted and incidental genomic research results to participants. Greater regulatory guidance is needed for a consistent approach.
IntroductionPain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents ...with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes.Methods and analysisThis will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are significant comorbidities, end-of-life status or enrolment in a concurrent pain study. The primary aim is to determine the effect of Pain Squad+, with and without nurse support, on pain intensity in adolescents with cancer, when compared with a waitlist control group. The secondary aims are to determine the immediate and sustained effect over time of using Pain Squad+, with and without nurse support, as per prospective outcome measurements of pain interference, HRQL, pain self-efficacy and cost. Linear mixed models with baseline scores as a covariate will be used. Qualitative interviews with adolescents from all trial arms will be conducted and analysed.Ethics and disseminationThis trial is approved by the Hospital for Sick Children Research Ethics Board. Results will provide data to guide adolescents with cancer and healthcare teams in treating pain. Dissemination will occur through partnerships with stakeholder groups, scientific meetings, publications, mass media releases and consumer detailing.Trial registration numberNCT03632343 (ClinicalTrials.gov).
There is an increasing demand for researchers to provide research results to participants. Our aim was to define an appropriate process for this, based on needs and attitudes of participants.
A ...multicenter survey in five sites in the United States and Canada was offered to parents of children with cancer and adolescents with cancer. Respondents indicated their preferred mode of communication of research results with respect to implications; timing, provider, and content of the results; reasons for and against providing results; and barriers to providing results.
Four hundred nine parents (including 19 of deceased children) and 86 adolescents responded. Most parents (n = 385; 94.2%) felt that they had a strong right to research results. For positive results, most wanted a letter or e-mail summary (n = 238; 58.2%) or a phone call followed by a letter (n = 100; 24.4%). If the results were negative, phone call (n = 136; 33.3%) or personal visits (n = 150; 36.7%) were preferred. Parents wanted the summary to include long-term sequelae and suggestions for participants (n = 341; 83.4%), effect on future treatments (n = 341; 83.4%), and subsequent research steps (n = 284; 69.5%). Understanding the researcher was a main concern about receiving results (n = 145; 35.5%). Parents felt that results provide information to support quality of life (n = 315; 77%) and raise public awareness of research (n = 282; 68.9%). Adolescents identified similar preferences.
Parents of children with cancer and adolescents with cancer feel strongly that they have a right to be offered research results and have specific preferences of how and what information should be communicated.
Despite recent improvements in outcomes, 40% of children with high-risk neuroblastoma will experience relapse, facing a guarded prognosis for long-term cure. Whether recurrences are at new sites or ...sites of original disease may guide decision making during initial therapy.
Eligible patients were retrospectively identified from institutional databases at first metastatic relapse of high-risk neuroblastoma. Included patients had disease involving metaiodobenzylguanidine (MIBG)-avid metastatic sites at diagnosis and first relapse, achieved a complete or partial response with no more than one residual MIBG-avid site before first relapse, and received no total body irradiation or therapy with (131)I-MIBG before first relapse. Anatomically defined metastatic sites were tracked from diagnosis through first relapse to determine tendency of disease to recur at previously involved versus uninvolved sites and to assess whether this pattern was influenced by site irradiation.
Of 159 MIBG-avid metastatic sites identified among 43 patients at first relapse, 131 (82.4%) overlapped anatomically with the set of 525 sites present at diagnosis. This distribution was similar for bone sites, but patterns of relapse were more varied for the smaller subset of soft tissue metastases. Among all metastatic sites at diagnosis in our subsequently relapsed patient cohort, only 3 of 19 irradiated sites (15.8%) recurred as compared with 128 of 506 (25.3%) unirradiated sites.
Metastatic bone relapse in neuroblastoma usually occurs at anatomic sites of previous disease. Metastatic sites identified at diagnosis that did not receive radiation during frontline therapy appeared to have a higher risk of involvement at first relapse relative to previously irradiated metastatic sites. These observations support the current paradigm of irradiating metastases that persist after induction chemotherapy in high-risk patients. Furthermore, they raise the hypothesis that metastatic sites appearing to clear with induction chemotherapy may also benefit from radiotherapeutic treatment modalities (external beam radiation or (131)I-MIBG).
Context
Empathy is vital to the physician–patient relationship. It promotes patient compliance and increases treatment efficacy. Studies evaluating the loss of empathy as residents advance through ...training curricula have generated inconsistent claims. Those considering diverse resident populations have supported a decline, whereas the few studies focused on paediatrics note stable empathy scores during training, which, indeed, exceed those of the general population. To better understand the issue as it pertains to paediatrics trainees, this study aimed to explore the state, and map a trajectory, of empathy in paediatrics residents, to identify factors influencing the learning and retention of empathy.
Methods
This qualitative descriptive study was conducted at an urban children's hospital in Canada. A total of 10 participants were recruited for semi‐structured interviews via a purposeful sampling strategy. The institutional research ethics board approved the project.
Results
Senior residents (R3 and R4) reported increased empathy, attributable to greater knowledge regarding paediatric illnesses, according them a fuller sense of the impact on families. Challenges to sustained empathy correlated with published literature: time constraints, compassion fatigue and burnout with poor coping, and the hidden curriculum. Empathy was learned from peers, preceptors and other health care providers. Resident resilience, borne out of personal adversity, was protective against the loss of empathy. Residents advocated for increased autonomy and responsibility for patient care, and increased exposure to longitudinal care, including the patient's social context and home life, to increase resident empathy.
Conclusions
Curriculum development committees could consider the inclusion of these encounters and experiences in residency training, although similar descriptive research in other specialty contexts would be needed to refine understanding.
We commonly criticize medical educational for how it extinguishes empathy in its trainees. Rawal et al. offer data suggesting reality may be more nuanced as pediatrics residents were seen to hold overlapping interpretations of empathy, acknowledge its value, and thoughtfully strive to practice it.
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