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Background: Selumetinib shrank inoperable symptomatic plexiform neurofibromas (PN) in children with neurofibromatosis type 1 (NF1) and provided clinical benefit for many in our previously published phase 1/2 clinical trials (SPRINT, NCT01362803). At the data cutoff (DCO) of the prior publications, 65% of participants were still receiving treatment. This report presents up to 5 years of additional safety and efficacy data from these studies., Methods: This manuscript includes data from the phase 1 and phase 2, stratum 1 study which included participants with clinically significant PN-related morbidity. Participants received continuous selumetinib dosing (1 cycle = 28 days). Safety and efficacy data through February 27, 2021 are included. PN response assessed by volumetric magnetic resonance imaging analysis: Confirmed partial response (cPR) ≥20% decrease from baseline on 2 consecutive evaluations. Phase 2 participants completed patient-reported outcome measures assessing tumor pain intensity (Numeric Rating Scale-11) and interference of pain in daily life (pain interference index)., Results: For the 74 children (median age 10.3 years; range 3-18.5) enrolled, overall cPR rate was 70% (52/74); median duration of treatment was 57.5 cycles (range 1-100). Responses were generally sustained with 59% (44) lasting ≥ 12 cycles. Tumor pain intensity (n = 19, P = .015) and pain interference (n = 18, P = .0059) showed durable improvement from baseline to 48 cycles. No new safety signals were identified; however, some developed known selumetinib-related adverse events (AEs) for the first time after several years of treatment., Conclusions: With up to 5 years of additional selumetinib treatment, most children with NF1-related PN had durable tumor shrinkage and sustained improvement in pain beyond that previously reported at 1 year. No new safety signals were identified; however, ongoing monitoring for known selumetinib-related AEs is needed while treatment continues., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2023.)

Plexiform Neurofibromas (PN) are a common manifestation of the genetic disorder neurofibromatosis type 1 (NF1). These benign nerve sheath tumors often cause significant morbidity, with treatment options limited historically to surgery. There have been tremendous advances over the past two decades in our understanding of PN, and the recent regulatory approvals of the MEK inhibitor selumetinib are reshaping the landscape for PN management. At present, there is no agreed upon PN definition, diagnostic evaluation, surveillance strategy, or clear indications for when to initiate treatment and selection of treatment modality. In this review, we address these questions via consensus recommendations from a panel of multidisciplinary NF1 experts., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefits for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low-grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

Background: Selumetinib was recently approved for the treatment of inoperable symptomatic plexiform neurofibromas (PNs) in children with neurofibromatosis type 1 (NF1). This parallel phase II study determined the response rate to selumetinib in children with NF1 PN without clinically significant morbidity., Methods: Children with NF1 and inoperable PNs, which were not yet causing clinically significant morbidity but had the potential to cause symptoms, received selumetinib at 25 mg/m2 orally twice daily (1 cycle = 28 days). Volumetric magnetic resonance imaging analysis and outcome assessments, including patient-reported (PRO), observer-reported, and functional outcome measures were performed every 4 cycles for 2 years, with changes assessed over time. A confirmed partial response (cPR) was defined as PN volume decrease of ≥20% on at least 2 consecutive scans ≥3 months apart., Results: 72% of subjects experienced a cPR on selumetinib. Participants received selumetinib for a median of 41 cycles (min 2, max 67) at data cutoff. Approximately half of the children rated having some target tumor pain at baseline, which significantly decreased by pre-cycle 13. Most objectively measured baseline functions, including visual, motor, bowel/bladder, or airway function were within normal limits and did not clinically or statistically worsen during treatment., Conclusions: Selumetinib resulted in PN shrinkage in most subjects with NF1 PN without clinically significant morbidity. No new PN-related symptoms developed while on selumetinib, and PRO measures indicated declines in tumor-related pain intensity. This supports that selumetinib treatment may prevent the development of PN-related morbidities, though future prospective studies are needed to confirm these results., Clinical Trial Registration: ClinicalTrials.gov NCT01362803., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.)

Background: Entrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non-small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors., Methods: STARTRK-NG (NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D., Results: At data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4)., Conclusions: Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

If health providers are aware of their patients' literacy skills, they can more appropriately tailor their communication with patients. Few providers, however, assess patient's literacy skills for fear of offending patients, but no research has ever determined if patients object to such assessments. Our objectives were to determine the percentage of patients seen for routine health care that would agree to undergo literacy assessment and if satisfaction of patients differs in practices that perform literacy assessments versus practices that do not. We randomized 20 private and public medical practices to an intervention group that implemented literacy assessments with the Newest Vital Sign and a control group that did not. For intervention practices, we noted the percentage of patients agreeing to undergo the assessment. For both intervention and control practices, we assessed patient satisfaction. Of 289 patients asked to undergo literacy assessment in the intervention practices, 284 (98.3%) agreed to do so, including 125 (46.1%) with low or possibly low literacy skills. There was no difference in satisfaction between the intervention group and the control group. We conclude that patients are willing to undergo literacy assessments during routine office visits and performing such assessments does not decrease patient satisfaction.

Purpose: The readability of consumer medication information (CMI) inserts accompanying intranasal corticosteroid (INCS) inhalers currently prescribed in the United States was studied., Methods: INCS inhalers were identified (n = 7) using Epocrates R(x) Pro and English- language CMI was obtained from each inhaler's manufacturer. The CMI was evaluated for reading grade level (using Fry's readability formula) and font size, dimensions (length and width), illustrations (diagrams and figures), and directions for use., Results: The mean +/- S.D. reading grade level of the CMI was 6.9 +/- 0.7 (range, 6-8). The mean +/- S.D. font size was 9.0 +/- 2.2 (range, 6-12). The mean +/- S.D. CMI page length and width were 31.3 +/- 22.5 cm and 14.0 +/- 12.9 cm, respectively. A device-overview figure was included in three of the seven educational samples. The mean size of illustrations was 7.9 cm(2) (range, 2.9-25.9 cm(2)), with a mean +/- S.D. of 7.6 +/- 3.2 (range, 3-11) figures per CMI insert. Directions followed a logical, step-by-step chronological sequence in every CMI insert., Conclusion: Most CMI for INCS inhalers is written at a reading level slightly higher than recommended, printed in a font size smaller than recommended, and illustrated inadequately for successful patient education.

Purpose: The effects of pictorial aids in medication instructions on medication recall, comprehension, and adherence are reviewed., Summary: Many patients depend on medication labels and patient information leaflets for pertinent drug information, but these materials are often difficult for patients to understand. Research in psychology and marketing indicates that humans have a cognitive preference for picture-based, rather than text-based, information. Studies have shown that pictorial aids improve recall, comprehension, and adherence and are particularly useful for conveying timing of doses, instructions on when to take medicine, and the importance of completing a course of therapy. Other research has compared various techniques for using picture-based information and supports the use of integrative instructions, a combination of textual, oral, and pictorial communication, to promote comprehension and adherence. While pictures have generally proven useful for improving patient comprehension and adherence, not all picture-based interventions have produced successful results. Some icons, particularly clock icons, have been found to be too complex to enhance understanding and could not overcome the advantage provided by the familiarity of the textbased format, suggesting that patients be trained to use pictorial medication information before they are expected to use icons as an aid for medication administration. In addition to enhancing understanding, pictorial aids have been found to improve patients' satisfaction with medication instructions., Conclusion: The use of pictorial aids enhances patients' understanding of how they should take their medications, particularly when pictures are used in combination with written or oral instructions.

Purpose: The suitability, readability, and cultural appropriateness of written supplemental materials available on the Internet for nonprescription medications were examined., Methods: We videotaped 48 hours of television programming, recording a total of 152 advertisements highlighting 37 unique nonprescription medications. The supplemental materials corresponding to each advertised medication were downloaded and printed in their entirety from each product-specific Web site. These materials were assessed using the Suitability Assessment of Materials (SAM) instrument. Total SAM scores were grouped as follows: not suitable (0-39%), adequate (40-69%), and superior (70-100%). The Fry readability formula was used to determine the reading grade level for the materials assessed with the SAM instrument., Results: The mean +/- S.D. SAM score of all materials was 54.9% +/- 0.1% (range, 38-76%). Materials for the majority of drugs (86.5%, n = 32) were rated adequate. Materials for four drugs (10.8%) were rated superior, and the material for one drug was not suitable. While the total SAM scores were adequate for most of the materials evaluated, the majority of materials scored particularly poorly for their reading level (the materials for 81.1% of drugs were not suitable). The materials for 40.9% of drugs used uncommon words., Conclusion: Evaluation of the suitability, readability, and cultural appropriateness of written supplemental materials for nonprescription medications available on manufacturer-sponsored Web sites and intended for consumers or patients revealed that SAM scores were adequate for most of the materials; however, many scored poorly in the areas of reading level and used uncommon words.