Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan (Trp) into downstream catabolites known as kynurenines. Coincidently, ...numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer. Preclinical studies have further introduced an interesting paradox: while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden, approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival. Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy, these data suggest that there is a more complex mechanism of action than previously appreciated. Similar to the dual faces of the astrological Gemini, we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism, as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects. The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration, but the lack of a universal prognostic significance among all cancer subtypes. Finally, ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients.
Seizures are a common complication of both primary central nervous system (CNS) tumors and other oncologic processes with CNS involvement. They occur most frequently during induction or consolidation ...therapy, but there is a growing body of evidence that they can also develop later in life. Refractory epilepsy can develop as a late complication for survivors of pediatric cancer with CNS involvement who undergo chemoradiation therapy.
We report three patients who presented with atypical nonconvulsive seizures (behavioral arrest, falls, nonsensical speech) up to 14 years after cancer diagnosis. All underwent whole-brain radiation in addition to chemotherapy. None had a prior epilepsy diagnosis or known prior seizures. One patient suddenly passed away of unclear causes five months after diagnosis, and the other two continued to have EEG findings consistent with cerebral dysfunction and epileptogenicity years after diagnosis.
We hypothesize that the development of refractory epilepsy may be a late effect of radiation treatment. Given the high morbidity and mortality associated with epilepsy, early identification is crucial to improve outcomes and quality of life for this vulnerable population. This is especially true for patients with medication-refractory epilepsy as there is an increasing breadth of effective surgical options.
Utilizing a Scoping Review strategy in the domain of immune biology to identify immune therapeutic targets, knowledge gaps for implementing immune therapeutic strategies for pediatric brain tumors ...was assessed. The analysis demonstrated limited efforts to date to characterize and understand the immunological aspects of tumor biology with an over-reliance on observations from the adult glioma population. Foundational knowledge regarding the frequency and ubiquity of immune therapeutic targets is an area of unmet need along with the development of immune-competent pediatric tumor models to test therapeutics and especially combinatorial treatment. Opportunities arise in the evolution of pediatric tumor classification from histological to molecular with targeted immune therapeutics.
A 6-year-old girl presented with a 1-week history of progressive upper and lower extremity weakness and bilateral upper extremity dysesthesia. Imaging demonstrated a 4.7 × 1.2-cm enhancing ...intramedullary lesion in the cervical spine from level C2 to C5 with associated cystic components and syringomyelia. The patient underwent a C2–C5 laminoplasty, with gross total resection of the intramedullary lesion. Histological analysis showed small to medium-sized epithelioid cells, with predominantly a solid architecture focally infiltrating into the adjacent spinal cord tissue. Focal papillary differentiation was present along with peri-vascular pseudorosettes, mucin microcysts, and globules of dense collagen. Focal anaplasia was noted with mitosis (5/10 HPF), focal necrosis, and elevated Ki67 10–15%. These findings were consistent with a myxopapillary ependymoma with anaplastic features. CSF cytology was negative for tumor cells. MYCN amplification was not present. She was treated with targeted proton-beam radiation therapy. This is the fourth case of an intramedullary anaplastic myxopapillary ependymoma to date, and the first case in the cervical spine reported in the literature.
Background
Children and adolescents with cancer may experience multiple disease- and treatment-related symptoms that negatively affect health-related quality of life. Routine symptom surveillance ...thus constitutes an important component of supportive care in pediatric oncology. The Symptom Monitoring and Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) system will administer, score, interpret, and display the results of symptom assessments captured weekly using patient-reported outcomes presented via the electronic health record (EHR) portal between clinic visits in oncology ambulatory settings, when patients are likely to be more symptomatic. This study is testing a digital system for routine symptom surveillance that includes EHR-based reports to clinicians and alerts for severe symptoms.
Objective
In this randomized trial, we are examining the effects of the SyMon-SAYS system on perceived barriers to symptom management, self-efficacy, and symptom severity. Better self-management and timely clinical intervention to address symptoms promote adherence to treatment plans, strengthen child and parent self-efficacy, improve interactions between children, parents, and their clinical providers, and optimize clinical outcomes.
Methods
The SyMon-SAYS system is integrated into the EHR to streamline the presentation of symptom scores and delivery of alerts for severe symptoms to clinicians using EHR (Epic) messaging functionalities. Children (aged 8 to 17 years) complete the weekly symptom assessment and review the symptom report by logging into the patient portal (Epic MyChart). This single-institution waitlist randomized controlled trial is recruiting 200 children (aged 8-17 years) with cancer and their parents, guardians, or caregivers. Participating dyads are randomly assigned to receive the intervention over 16 weeks (Group A: 16-week SyMon-SAYS intervention; Group B: 8-week usual care and then an 8-week SyMon-SAYS intervention). Analyses will (1) evaluate the efficacy of SyMon-SAYS at week 8 and the maintenance of those effects at week 16; (2) evaluate factors associated with those efficacy outcomes, including contextual factors, adherence to the SyMon-SAYS intervention, demographic characteristics, and clinical factors; and (3) evaluate predictors of adherence to the SyMon-SAYS intervention and preference of SyMon-SAYS versus usual care.
Results
Data collection is currently in progress. We hypothesize that at 8 weeks, those receiving the SyMon-SAYS intervention will report decreased parent-perceived barriers to managing their children’s symptoms, increased parent and child self-efficacy, decreased child symptom burden, and ultimately better child health-related quality of life, compared to waitlist controls. Feasibility, acceptability, and engagement from the perspectives of the children with cancer, their parents, and their clinicians will be examined using mixed methods.
Conclusions
We anticipate that this system will facilitate prompt identification of problematic symptoms. Additionally, we hypothesize that with the availability of graphical symptom reports over time, and timely provider responses, children or parents will become better informed and take an active role in managing their symptoms, which will further improve clinical outcomes.
Trial Registration
ClinicalTrials.gov NCT04789720; https://clinicaltrials.gov/study/NCT04789720
International Registered Report Identifier (IRRID)
DERR1-10.2196/50993
Abstract BACKGROUND Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. Frequency of neuroimaging varies with no ...standardized approach. METHODS A single institution retrospective cohort study evaluated frequency and pattern of recurrences. Pediatric patients (birth to age 21 years) diagnosed with a primary CNS tumor between 1988 and 2011 treated at Lurie Children’s Hospital were included. RESULTS This study included 476 patients; the majority diagnosed with a low-grade glioma (LGG) (n=138; 29%), high grade glioma (HGG) (n=77; 16%), ependymoma (n=70; 15%) or medulloblastoma (n=61; 13%). LGG, HGG and ependymoma patients more commonly had multiply recurrent disease (p=0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs 32%; p=<0.01). Treatment at relapse included surgical managment more often than non-surgical approach (59% vs. 41%; p=0.0016) in patients, leading to pathology confirmation of recurrence. Mean time to first relapse for the entire cohort was 2.5 years (range 1 day-24.8 years). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7 months) whereas those with Atypical Teratoid Rhabdoid Tumor and Choroid plexus carcinoma tended to have the shortest time to relapse (8.9 months and 9 months, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis, including those diagnosed with LGG, medulloblastoma, pineoblastoma, craniopharyngioma, GCT, and meningioma. CONCLUSION With a higher percentage of tumor recurrence/progression seen on neuroimaging before development of symptoms, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. While the study is limited since we did not look at overall survival, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.
Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. The frequency of neuroimaging surveillance varies without a ...standardized approach. A single-institutional retrospective cohort study evaluated the frequency of recurrences. This study included 476 patients with the majority diagnosed with low-grade glioma (LGG) (n=138, 29%), high-grade glioma (HGG) (n=77, 16%), ependymoma (n=70, 15%), or medulloblastoma (n=61, 13%). LGG, HGG, and ependymoma patients more commonly had multiply recurrent disease ( P =0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs. 32%; P =<0.01). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7 mo) whereas those with atypical teratoid rhabdoid tumor and choroid plexus carcinoma tended to have the shortest time to relapse (8.9 and 9 mo, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis. With a higher tendency toward detection of tumor recurrence/progression on MRI surveillance in comparison to clinical progression, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. With some relapses >10 years from initial diagnosis, imaging beyond this time point may be useful in particular tumor types. While the study is limited in outcome analysis, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.
Abstract BACKGROUND The gift of post-mortem tissue donation is a critical resource in the discovery and interrogation of pathobiological mechanisms of pediatric brain tumors. Broad generalizability ...of research findings requires a representative population to participate in pre-clinical studies. As a “Center of Excellence” within the Gift from a Child initiative, our institution has a well-established post-mortem tissue donation program funded by the Swifty Foundation. Our primary objective was to determine if clinical and socioeconomic differences exist between patients that participated in and those that declined research-based autopsy. METHODS We performed a single-institution retrospective chart review of pediatric patients with central nervous system (CNS) malignancies who died from their disease between 1/1/2021 and 12/31/2022. Individual clinical, demographic, and socioeconomic data were assessed. Population-level data were estimated using Zip Code Tabulation Areas. Descriptive statistics were used to compare categorical data. RESULTS Among 26 patients who died secondary to disease in the study timeframe, 23 (88%) were approached and 8/23 (35%) consented to participation. In the consented group (C) vs. declined group (D), there was a higher percentage of White, Non-Hispanic/Latino patients by self-reported race (C: 88% vs. D: 55%) and no patients who identified as Asian or Hispanic/Latino (C: 0% & 0% vs. D: 13% & 27%). Of all patients approached, 2 required interpreters (9%) and both families declined participation. The rate of private insurance was higher in the consented group (C: 75% vs D: 47%) compared to Medicaid as primary insurance in the declined group (C: 13% vs D: 53%). CONCLUSIONS Patients from racial and ethnic minorities are underrepresented in tissue donation programs. Future research should aim to understand and improve identified disparities to ensure advancements benefit all children with CNS malignancies. One area we plan to address is improved communication with non-English speaking families by educating interpreter services prior to discussion.
Abstract
AIMS
The unrelieved symptoms and side effects of often-aggressive cancer treatments can lead to poor outcomes. SyMon-SAYS was developed to minimize symptom management barriers and symptom ...burdens by routinely collecting and interpreting patient-reported outcomes in pediatric oncology ambulatory settings. This paper reports the preliminary results of the 16-week SyMon-SAYS trial.
METHODS
Children (ages 8-17) with cancer (on-therapy or within 6-M post-treatment) were randomly assigned to either intervention (IG; weeks 1-16 intervention) or waitlist (WG; weeks 1-8 waitlist, weeks 9-16 intervention) group. Children in the intervention phase reported on 9 symptoms (fatigue, sadness, itch, pain, worry, appetite, nausea, sleep, headache) weekly via an electronic medical record patient portal. Scores exceeding a pre-defined threshold triggered an alert to the treatment team. Parents completed a symptom management barriers questionnaire (SMBQ) at baseline, weeks 8 (primary time-point and analyzed in this paper) and 16. Mixed-effects models were used to evaluate symptom burden over time.
RESULTS
Data from 75 children (37 IG, 38 WG) were analyzed (mean age=13.3 years, 58.8% male, 74.7% white). Of them, 43.9% had leukemia, and 17.5% brain tumor. On average, the IG completed 11 (possible min=0 max=16) and the WG completed 5 (possible min=0 max=8) symptom checklists; of them, 60% triggered symptom alerts. Results of the mixed-effects models showed significantly (p< 0.05) improvement in fatigue, sadness, worry, appetite and headache. No significant changes were found on others. For SMBQ, IG parents reported significantly in favor of “enough time with my child's doctors/nurses to talk about symptoms” than WG parents from baseline to week 8. No significant differences between IG and WG over time on other SMBQ items.
CONCLUSIONS
Our preliminary findings showed SyMon-SAYS alleviated emotional related symptoms over time. Physical symptoms might be related more to disease severity and treatment intensity, which we plan to investigate when more data is available.
Abstract
Unrelieved symptom burden due to cancer treatments can lead to poor psychosocial functioning and decreased health-related quality of life (HRQOL) for patients and their families. Barriers at ...the patient, healthcare provider and system levels can contribute to poor symptom management. Funded by the US National Cancer Institute, we have developed the Symptom Monitoring & Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) program. SyMon-SAYS is a technology-based program with the potential to minimize symptom management barriers by routinely collecting and interpreting patient-reported outcomes in pediatric oncology ambulatory settings in a manner that is efficient, actionable by clinicians, supports engagement of patients and families with their health and care, and improves clinical processes and outcomes. This is a single institution modified waitlist control 16-week randomized trial of 200 children (ages 8-17) with cancer and their parents/guardians. Participants in the intervention phase will complete a symptom checklist weekly via the electronic health record patient portal. Scores exceeding a pre-defined threshold will trigger an alert to the treatment team, which will review the report and take appropriate actions. Participants will complete a separate battery of questionnaires assessing HRQOL at baseline and weeks 8 and 16. The recruitment is in progress. As of today, we have recruited 57 patients/parents. 29 completed 16-week study (15 intervention & 14 wait-list). Preliminary results showed SyMon-SAYS system was easy (92%) and convenient (85%) to use. Parents were satisfied (74.1%) with the SyMon-SAYS program. Comparing to the waitlist control, intervention group parents reported significantly less concerns on not having enough time to discuss their child’s symptoms with treating clinicians (p=0.0022), and disagreed that it is not necessary to treat their child’s symptoms as they will go away (p=0.04). We anticipate completing the recruitment by the end of 2023.
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