Neuro-Oncology Practice Clinical Debate: long-term antiepileptic drug prophylaxis in patients with glioma.
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ABSTRACT:
SUBMITTER: Stocksdale B
PROVIDER: S-EPMC7716178 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The treatment of children with low-grade glioma has evolved over the last several decades, beginning initially with focal radiotherapy, which has now been largely replaced by systemic treatment with conventional chemotherapy agents or more recently molecularly targeted therapeutics. A consensus standard of care is not well defined, leaving clinicians and parents to choose from an increasing number of options, often without complete information concerning the associated risks and benefits. Issues critical to this topic include timing of interventions (when to treat), preservation of neurological function (goals of treatment), choice of initial therapy strategy (conventional cytotoxic chemotherapy vs molecularly targeted therapy), duration of treatment (how long, and what clinical or imaging endpoints to consider), and perhaps most important, risk reduction relative to anticipated benefit. The groups from the University of California, San Francisco and Dana Farber Cancer Institute, moderated by Michael Prados, herein debate the merits of cytotoxic chemotherapy and targeted therapeutics as initial treatment strategies in pediatric low-grade glioma, a topic discussed daily in Tumor Boards across the United States and abroad. Prospective, randomized, phase 3 trials comparing the 2 strategies, conducted within homogenous disease settings, with consistently evaluated functional and imaging endpoints, are not available to guide the risks/benefit discussion. As is often the case in rare biologically diverse diseases, in a vulnerable population, therapy decisions are frequently based on incomplete data, physician experience, bias to some degree, and patient/family preference.
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Project description:Gliomas are the most common intrinsic brain tumor in adults. Although maximal tumor resection improves survival, this must be balanced with preservation of neurologic function. Technological advancements have greatly expanded our ability to safely maximize tumor resection and design innovative therapeutic trials that take advantage of intracavitary delivery of therapeutic agents after resection. In this article, we review the role of surgical intervention for both low-grade and high-grade gliomas and the innovations that are driving and expanding the role of surgery in this therapeutically challenging group of malignancies.
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Project description:Primary CNS tumors are the leading cause of cancer-related death in pediatrics. It is essential to understand treatment trends to interpret national survival data. In Canada, children with CNS tumors are treated at one of 16 tertiary care centers. We surveyed pediatric neuro-oncologists to create a national standard of practice to be used in the absence of a clinical trial for seven of the most prevalent brain tumors in children. This allowed description of practice across the country, along with a consensus. This had a multitude of benefits, including understanding practice patterns, allowing for a basis to compare in future research and informing Health Canada of the current management of patients. This also allows all children in Canada to receive equivalent care, regardless of location.
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Project description:Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity. Currently, RNA-seq is beginning to be incorporated into regular neuro-oncology practice in the form of precision neuro-oncology programs, which use information from tumor sequencing to guide implementation of personalized targeted therapies. These programs show great promise in improving patient outcomes for tumors where single agent trials have been ineffective. As RNA-seq is a relatively new technique, many further applications yielding new advances in CNS tumor research and management are expected in the coming years.
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Project description:Tumor predisposition syndromes may be under-recognized in neuro-oncology practice. Identifying patients with a hereditary tumor predisposition permits appropriate tumor management as well as surveillance and risk-reduction measures for patients and their families. The American College of Medical Genetics and Genomics and the National Society of Genetic Counselors recently published referral guidelines for tumor predisposition assessment, providing an impetus to review the use of genetic counseling in neuro-oncology and to describe features of the less stereotypic conditions from the perspective of neuro-oncology practice. This review also provides a framework for the identification and management of these conditions, as well as references to guidelines and resources for providers and patients.
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Project description:ObjectiveTo examine the relationship between previously identified nonadherence trajectories during the first 6 months of antiepileptic drug (AED) therapy and long-term seizure-free rates (defined as ≥1 year of seizure freedom at the 4 years postdiagnosis milestone) in a cohort of children with newly diagnosed epilepsy.MethodsA prospective longitudinal observational study of AED adherence and seizure freedom in a consecutive cohort of 124 children (ages 2-12 years) with newly diagnosed epilepsy was conducted. The association between previously identified AED adherence trajectories (i.e., near-perfect adherence [e.g., average adherence = 96.8%] vs nonadherent) and seizure freedom for ≥1 year at the 4 years postdiagnosis milestone was determined.ResultsChildren who exhibited nonadherence to AED therapy in the first 6 months of treatment were 3.24 times more likely not to have achieved ≥1 year of seizure freedom at the 4 years postdiagnosis milestone compared to children in the near-perfect adherence group (χ² = 5.13; p = 0.02). Specifically, at the 4 years postdiagnosis milestone, only 12% of children in the near-perfect adherence group were continuing to experience seizures compared to 31% of children in the nonadherent group.ConclusionsChildren with epilepsy who achieved near-perfect adherence during the first 6 months of therapy experienced a higher rate of seizure freedom 4 years postdiagnosis compared with those children who demonstrated early nonadherence. This suggests that adherence intervention early in the course of treatment could play a role in improving long-term seizure freedom rates in children with epilepsy.
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Project description:ObjectiveContemporary management of patients with neuro-oncologic disease requires an understanding of approvals by the US Food and Drug Administration (FDA) related to nervous system tumors. To summarize FDA updates applicable to neuro-oncology practitioners, we sought to review oncology product approvals and Guidances that were pertinent to the field in the past year.MethodsOncology product approvals between January 1, 2020, and December 31, 2020, were reviewed for clinical trial outcomes involving tumors of the nervous system. FDA Guidances relevant to neuro-oncology were also reviewed.ResultsFive oncology product approvals described outcomes for nervous system tumors in the year 2020. These included the first regulatory approval for neurofibromatosis type 1: selumetinib for children with symptomatic, inoperable plexiform neurofibromas. Additionally, there were 4 regulatory approvals for non-central nervous system (CNS) cancers that described clinical outcomes for patients with brain metastases. These included the approval of tucatinib for metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer including patients with brain metastases, brigatinib for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), and pralsetinib and selpercatinib for RET fusion-positive NSCLC. Finally, two FDA Guidances for Industry, "Cancer Clinical Trial Eligibility Criteria: Brain Metastases" and "Evaluating Cancer Drugs in Patients with Central Nervous System Metastases" were published to facilitate drug development for and inclusion of patients with CNS metastases in clinical trials.ConclusionsDespite the challenges of the past year brought on by the COVID-19 pandemic, progress continues to be made in neuro-oncology. These include first-of-their-kind FDA approvals and Guidances that are relevant to the management of patients with nervous system tumors.
| S-EPMC8218275 | biostudies-literature
Project description:PurposeOptimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide.MethodsIn this multicenter study we retrospectively analyzed data of patients with diffuse grade 2-4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity.ResultsWe included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26-51%) versus 30% (95%CI 20-41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46-1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide.ConclusionLamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.
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Project description:ObjectivesMRI remains the preferred imaging investigation for glioblastoma. Appropriate and timely neuroimaging in the follow-up period is considered to be important in making management decisions. There is a paucity of evidence-based information in current UK, European and international guidelines regarding the optimal timing and type of neuroimaging following initial neurosurgical treatment. This study assessed the current imaging practices amongst UK neuro-oncology centres, thus providing baseline data and informing future practice.MethodsThe lead neuro-oncologist, neuroradiologist and neurosurgeon from every UK neuro-oncology centre were invited to complete an online survey. Participants were asked about current and ideal imaging practices following initial treatment.ResultsNinety-two participants from all 31 neuro-oncology centres completed the survey (100% response rate). Most centres routinely performed an early post-operative MRI (87%, 27/31), whereas only a third performed a pre-radiotherapy MRI (32%, 10/31). The number and timing of scans routinely performed during adjuvant TMZ treatment varied widely between centres. At the end of the adjuvant period, most centres performed an MRI (71%, 22/31), followed by monitoring scans at 3 monthly intervals (81%, 25/31). Additional short-interval imaging was carried out in cases of possible pseudoprogression in most centres (71%, 22/31). Routine use of advanced imaging was infrequent; however, the addition of advanced sequences was the most popular suggestion for ideal imaging practice, followed by changes in the timing of EPMRI.ConclusionVariations in neuroimaging practices exist after initial glioblastoma treatment within the UK. Multicentre, longitudinal, prospective trials are needed to define the optimal imaging schedule for assessment.Key points• Variations in imaging practices exist in the frequency, timing and type of interval neuroimaging after initial treatment of glioblastoma within the UK. • Large, multicentre, longitudinal, prospective trials are needed to define the optimal imaging schedule for assessment.
| S-EPMC8043861 | biostudies-literature
Project description:BackgroundThe Children's Oncology Group (COG) has endorsed a clinical practice guideline (CPG) for acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis in children with cancer. This project aims to describe current acute CINV prophylaxis practice at COG sites and the gap between this practice and CPG recommendations.ProcedureTwo surveys were developed. The first survey, sent to 94 cancer control and supportive care responsible individuals (CCL RIs) at 94 COG institutions, asked if the institution had a standardized approach to practice and focused on antiemetic agent choice. The second survey, sent to 54 pharmacists at COG sites where the CCL RI indicated that there was a standardized approach to CINV prophylaxis practice, focused on antiemetic dosing. Survey results were described and analyzed for consistency with the CPG recommendations.ResultsAmong the 69 respondents to the first survey, 54 (78%) stated that their institutions have a standardized approach to CINV prophylaxis practice. However, antiemetic choice varied widely among respondents. Results from the 36 respondents to the second survey also demonstrated significant antiemetic dosing practice variability. Frequent sources of deviation from CPG recommendations were as follows: antiemetic choice when corticosteroids are contraindicated, dexamethasone dosing, aprepitant use in children less than 12 years, and aprepitant use in the presence of a known or suspected drug interaction.ConclusionsThere is a great diversity in the CINV prophylaxis provided to children with cancer at COG sites. Concerted strategies are required to improve awareness of the current CINV prophylaxis CPG and to facilitate CPG-consistent CINV prophylaxis.
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