6 results on '"Jane E, Minturn"'
Search Results
2. Vinblastine/Methotrexate for Debilitating and Progressive Plexiform Neurofibroma in Children and Young Adults with Neurofibromatosis Type 1: A Phase 2 Study
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Chelsea Kotch, Kristina Wagner, J. Harris Broad, Eva Dombi, Jane E. Minturn, Peter Phillips, Katherine Smith, Yimei Li, Ian N. Jacobs, Lisa M. Elden, Michael J. Fisher, and Jean Belasco
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Cancer Research ,Oncology ,plexiform neurofibroma ,neurofibromatosis type 1 ,chemotherapy ,clinical trial - Abstract
Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m2 and MTX 30 mg/m2 weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3–20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation.
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- 2023
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3. Efficacy of nivolumab in pediatric cancers with high mutation burden and mismatch-repair deficiency
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Anirban Das, Uri Tabori, Lauren C. Sambira Nahum, Natalie B. Collins, Rebecca Deyell, Rina Dvir, Cecile Faure-Conter, Timothy E. Hassall, Jane E. Minturn, Melissa Edwards, Elissa Brookes, Vanessa Bianchi, Adrian Levine, Simone C. Stone, Sumedha Sudhaman, Santiago Sanchez-Ramirez, Ayse B. Ercan, Lucie Stengs, Jiil Chung, Logine Negm, Gad Getz, Yosef E. Maruvka, Birgit Ertl-Wagner, Pamela S. Ohashi, Trevor Pugh, Cynthia Hawkins, Eric Bouffet, and Daniel A. Morgenstern
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Cancer Research ,Oncology - Abstract
Purpose: Checkpoint-inhibitors have limited efficacy for children with unselected solid and brain tumors. We report the first prospective pediatric trial (NCT02992964) using nivolumab exclusively for refractory non-hematological cancers harboring tumor mutation burden (TMB) ≥5 mutations/megabase (mut/Mb) and/or mismatch-repair deficiency (MMRD). Patients and methods: Twenty patients were screened, and ten ultimately included in the response cohort of whom nine had TMB >10mut/Mb (three initially eligible based on MMRD) and one patient had TMB between 5-10 mut/Mb. Results: Delayed immune responses contributed to best overall response of 50%, improving on initial objective responses (20%) and leading to 2-year overall survival (OS) of 50% (95% CI; 27, 93). Four children, including three with refractory malignant gliomas are in complete remission at a median follow-up of 37-months (range: 32.4-60), culminating in 2-year OS of 43% (95% CI; 18.2, 100). Biomarker analyses confirmed benefit in children with germline MMRD, microsatellite instability, higher activated and lower regulatory circulating T-cells. Stochastic mutation accumulation driven by underlying germline MMRD impacted the tumor microenvironment, contributing to delayed responses. No benefit was observed in the single patient with a MMR-proficient tumour and TMB 7.4 mut/Mb. Conclusions: Nivolumab resulted in durable responses and prolonged survival for the first time in a pediatric trial of refractory hypermutated cancers including malignant gliomas. Novel biomarkers identified here need to be translated rapidly to clinical care to identify children who can benefit from checkpoint-inhibitors, including for upfront management of their cancers.
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- 2023
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4. Guideline for Children With Cancer Receiving General Anesthesia for Procedures and Imaging
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Kaitlin J, Devine, Caroline, Diorio, Sarah A, Richman, Alicia A, Henderson, Katelyn, Oranges, Erin, Armideo, Michelle S, Kolb, Jason L, Freedman, Richard, Aplenc, Michael J, Fisher, Jane E, Minturn, Timothy, Olson, Rochelle, Bagatell, Lamia, Barakat, Colleen, Croy, Jane, Mauro, Lisa, Vitlip, Michael R, Acord, Peter, Mattei, Victoria K, Johnson, Conor M, Devine, Caroline, Pasquariello, and Anne F, Reilly
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Diagnostic Imaging ,Consensus ,Oncology ,Neoplasms ,Pediatrics, Perinatology and Child Health ,Hematopoietic Stem Cell Transplantation ,Humans ,Hematology ,Anesthesia, General ,Child - Abstract
Children with cancer and those undergoing hematopoietic stem cell transplantation frequently require anesthesia for imaging as well as diagnostic and therapeutic procedures from diagnosis through follow-up. Due to their underlying disease and side effects of chemotherapy and radiation, they are at risk for complications during this time, yet no published guideline exists for preanesthesia preparation. A comprehensive literature review served as the basis for discussions among our multidisciplinary panel of oncologists, anesthesiologists, nurse practitioners, clinical pharmacists, pediatric psychologists, surgeons and child life specialists at the Children's Hospital of Philadelphia. Due to limited literature available, this panel created an expert consensus guideline addressing anesthesia preparation for this population.
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- 2022
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5. Volumetric endpoints in diffuse intrinsic pontine glioma: comparison to cross-sectional measures and outcome correlations in the International DIPG/DMG Registry
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Margot A Lazow, Martijn T Nievelstein, Adam Lane, Pratiti Bandopadhayhay, Mariko DeWire-Schottmiller, Maryam Fouladi, John W Glod, Robert J Greiner, Lindsey M Hoffman, Trent R Hummel, Lindsay Kilburn, Sarah Leary, Jane E Minturn, Roger Packer, David S Ziegler, Brooklyn Chaney, Katie Black, Peter de Blank, and James L Leach
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Cancer Research ,Cross-Sectional Studies ,Glutamates ,Oncology ,Diffuse Intrinsic Pontine Glioma ,Brain Stem Neoplasms ,Humans ,Glioma ,Registries ,Neurology (clinical) ,Astrocytoma ,Pediatric Neuro-Oncology - Abstract
Background Cross-sectional tumor measures are traditional clinical trial endpoints; however volumetric measures may better assess tumor growth. We determined the correlation and compared the prognostic impact of cross-sectional and volumetric measures of progressive disease (PD) among patients with DIPG. Methods Imaging and clinical data were abstracted from the International DIPG Registry. Tumor volume and cross-sectional product (CP) were measured with mint Lesion™ software using manual contouring. Correlation between CP and volume (segmented and mathematical [ellipsoid] model) thresholds of PD were assessed by linear regression. Landmark analyses determined differences in survival (via log-rank) between patients classified as PD versus non-PD by CP and volumetric measurements at 1, 3, 5, 7, and 9 months postradiotherapy (RT). Hazard ratios (HR) for survival after these time points were calculated by Cox regression. Results A total of 312 MRIs (46 patients) were analyzed. Comparing change from the previous smallest measure, CP increase of 25% (PD) correlated with a segmented volume increase of 30% (R2 = 0.710), rather than 40% (spherical model extrapolation). CP-determined PD predicted survival at 1 month post-RT (HR = 2.77), but not other time points. Segmented volumetric-determined PD (40% threshold) predicted survival at all imaging timepoints (HRs = 2.57, 2.62, 3.35, 2.71, 16.29), and 30% volumetric PD threshold predicted survival at 1, 3, 5, and 9 month timepoints (HRs = 2.57, 2.62, 4.65, 5.54). Compared to ellipsoid volume, segmented volume demonstrated superior survival associations. Conclusions Segmented volumetric assessments of PD correlated better with survival than CP or ellipsoid volume at most time points. Semiautomated tumor volume likely represents a more accurate, prognostically-relevant measure of disease burden in DIPG.
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- 2022
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6. EOLP-04. A CALL TO ACTION TO INCREASE ACCESS TO POST-MORTEM BRAIN TUMOR DONATIONS: GIFT FROM A CHILD
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Nicole Lyons, Angela Waanders, Melissa Williams, Javad Nazarian, Augustine Eze, Miriam Bornhorst, Elizabeth Frenkel, Jennifer Mason, Jane E Minturn, Mateusz Koptyra, Michelle Monje, Jared Hysinger, Mark Souweidane, Jeffery P Greenfield, Cindy Campbell, Esteban Uceda, Amy Smith, Julia Hegert, Stephani Campion, Ginny McLean, Patti Gustafson, and Allen Gustafson
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
Implementation of access to donate post mortem tissue among pediatric brain tumor patients remains a challenge[DSM1] . Previous attempts to develop a post-mortem network have been jeopardized by barriers such as a lack of education, logistical coordination of donation, and difficulties effectively communicating the benefit of post-mortem donations to families. [CC2] Utilizing feedback from patients’ families, clinicians, and researchers, standard operating procedures (SOP) were developed and utilized by six “tissue navigators” (TN) working across institutions. Tissue navigators are critical in implementation of access to donate as they serve as a liaison between patients’ families and clinical team to ensure post-mortem tissue is procured correctly and respectfully. From 2018 through 2021, there has been an increase in donations, which has led to establishment of tumor cell cultures translating rapidly to clinical development, and a growing network of centers participating in GFAC procedures. Donations have been facilitated at over 75 institutions. GFAC has coordinated 146 donations in this 3-year launch timeframe, with nearly half from families outside GFAC’s primary institutional network. Barriers to implementation were addressed with the design of GFAC’s SOPs, which lead to the successful implementation of access to donation. GFAC is developing CME training for clinicians and researchers to address communication of post-mortem donation, continuing awareness campaigns with collaborators in the field, advocating for families to receive feedback on the donation, and expanding on the SOPs as more is learned from clinicians and families.
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- 2022
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