bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hematology/oncology outpatient perspectives on telehealth one year into the COVID-19 pandemic.
Authors: Blaes Anne Hudson , Jewett Patricia , Holtan Shernan , Lindgren Bruce , Hui Jane , Boucher Alexander Albert 
Published: June 2022

1594 Background: Telehealth use expanded during the COVID-19 pandemic, but few studies have explored patient perspectives on it after the initial months. Using mixed methods, we aimed to understand patient telehealth perspectives and to examine for whom telehealth is less optimal. Methods: A modified Telemedicine Satisfaction and Usefulness Questionnaire (TSUQ) for hematology/oncology outpatient care was sent to patients ≥18 years old within the M Health Fairview Masonic Cancer Clinic with ≥1 prior telehealth visit (phone and/or video). Two focus groups were also conducted. We summarized cohort characteristics and views on telehealth. We dichotomized selected TSUQ items (measured on a 1-5 scale) and evaluated them using logistic regression, adjusted for age (<65 years, ≥65 years), gender, race (White, other), income (<$50,000, $50,000-99,000, ≥$100,000, prefer not to say), education (no college degree, at least college degree), and having cancer (yes, no). Focus group data were analyzed qualitatively. Results: Of 7848 invitations, 588 surveys were completed (7.5% response rate). For respondents, 71% were female, 68.7% married/partnered, 90.6% identified as White, and 36.1% had a graduate/professional degree with an annual salary ≥$150,000 (21%). Most had cancer (73.3%) but were not currently receiving treatment (36.5%); 40% each had employer-based insurance or Medicare. Focus group members (n = 16) were chosen from a demographic mix of 121 volunteers. Most survey respondents found telehealth satisfactory [mean 3.8 ± standard deviation (SD) 0.9] and easy to use (mean 3.4 ± SD 0.9), 72.2% found it convenient, and 82.2% agreed that it saved time. Most (78.6%) would be happy with a combination of telehealth and in-person care going forward, but those with cancer were less likely to prefer future telehealth care (adjusted odds ratio [OR] 0.52, 95% confidence interval [CI] 0.34 - 0.81). Being male and having lower incomes were associated with greater telehealth satisfaction, (male vs. female, OR 1.68, 95% CI 1.00 - 2.83), income <$50,000 vs. ≥$100,000 (OR 2.47, 95% CI 1.16 - 5.28). Focus group members reported between 1 - 30 telehealth visits (overall care range 8 months - 30 years). Views on telehealth mirrored survey results. Time saved and reduced exposure risk were beneficial, especially for those in rural settings and for those seeing genetic counselors or palliative care. However, concerns were voiced about fewer in-person interactions, communication gaps, and provider style variability. Conclusions: Our findings show that oncology patients prefer care in person despite telehealth’s benefits. Additional work is needed to ascertain the optimal, and possibly patient subgroup-specific, combination of in-person and telehealth in ambulatory hematology/oncology care to manage the needs of different populations.
Multi-institutional randomized phase 3 trial comparing cancer stem cell-targeted versus physician-choice treatments in patients with recurrent high-grade gliomas (NCT03632135).
Authors: Ranjan Tulika , Sengupta Soma , Glantz Michael J. , Lu-Emerson Christine , Green Richard M. , Howard Candace M. , Yu Alexander , Chen Ricky , Chaudhary Rekha T. , Aregawi Dawit , Glass Jon , Mammoser Aaron Gerald , Moulding Hugh , Jubelirer Steven , Schroeder Jason , Anderson Mark Daniel , Lirette Seth T. , Alberico Anthony , Valluri Jagan , Claudio Pier Paolo 
Published: June 2022

2028 Background: Clinical outcomes in patients with recurrent high-grade glioma (HGG) remain poor. Cancer stem cells (CSCs) have been implicated in metastasis, treatment resistance and recurrence of HHGs. We have shown in several clinical studies that anti-CSC-directed therapy selected by ChemoID assay provides benefits in many cancer types; however, this is the first report of a randomized clinical trial evaluating whether CSC-targeted cytotoxic agents selected by ChemoID assay-guided therapy improves survival in patients with recurrent HGG. Methods: In this parallel-group, randomized, phase-3 clinical trial, patients at 13 clinical sites in the USA with grade-III/IV recurrent glioma (2016 WHO guidelines) were randomized 1:1 to either ChemoID assay-guided therapy or physician-choice therapy, and then treated and followed until unacceptable toxic effects, hospice, or death. The primary endpoint was overall survival (OS). Results: Combined median follow-up was 9 months. Median OS (mOS) was 12.5 months (95% CI, 10.2-14.7) in the ChemoID assay-guided group vs 9 months (95% CI, 4.2-13.8) in the physician-choice group (log-rank P =.010). Risk of death was significantly lower in the ChemoID assay group (HR = 0.44; 95% CI, 0.24-0.81; P =.008). Median progression free survival (PFS) was 10.1 vs 3.5 months (95% CI, 4.8-15.4 vs 1.9-5.1) (HR, 0.25; 95% CI, 0.14-0.44; P <.001). Conclusions: Primary endpoint was met in this randomized clinical trial. The mOS was 3.5 months longer in the ChemoID assay-guided group vs the physician-choice group. Clinical trial information: NCT03632135.
Investigating the impact of NGS data availability on clinical decision-making in brain cancer.
Authors: Eckburg Adam , John Jordan , Kumthekar Priya 
Published: June 2022

2032 Background: Next-generation sequencing (NGS) of cancer specimens is a valuable diagnostic tool that can provide detailed information regarding specific somatic genetic alterations within a tumor with potential for targeted treatment. Despite the increasing availability of NGS, preliminary data by John et al. from ASCO 2021 suggested that clinical decision making is not frequently impacted by NGS results in the setting of glioblastoma. Herein, we report how NGS data impacts other primary tumor types, including astrocytoma, oligodendroglioma, and various rare subtypes. Methods: A retrospective chart review was performed to assess the proportion of brain cancer patients receiving targeted treatment instead of standard therapeutics after NGS sequencing. Pertinent medical information was ascertained from Epic and the Electronic Data Warehouse. Targeted treatments were defined as those recommended by the Tempus report for NGS-identified potentially actionable mutations. Patients were stratified into one of three categories: astrocytoma, oligodendroglioma, or other rare subtypes (including meningioma, ependymoma, ganglioma, pleomorphic xanthoastrocytoma, atypical teratoid rhabdoid tumors, glioneuronal tumors, and CNS lymphomas). Results: Of 44 Astrocytoma patients with potentially actionable mutations, four (9.1%) were treated with targeted therapy in the form of Enasidenib, ONC201, Nivolumab, and Depatuxizumab, while 40 received NGS agnostic treatment. In 37 Oligodendroglioma patients, three (8.1%) were treated with either targeted Vorasidenib or Ivosidenib, while 34 were started on NGS agnostic therapies. Lastly, four (10.0%) of 40 patients with other rare primary tumor types received either Ibrutinib, Dabrafenib+Trametinib, Vigabatrin, or Vemurafenib as targeted therapy. Avastin and/or standard Temozolomide chemotherapy were the most common NGS agnostic therapies employed by clinicians across all three subclasses. Conclusions: Although a substantial number of potentially actionable mutations were detected by NGS, the presence of this data paired with Tempus targeted recommendations rarely impacted clinician decision-making, ranging from 8.1-10.0% of the time. Despite the availability of resources to prescribe targeted treatment, providers consistently chose NGS agnostic therapies instead. Utilization of targeted treatment may become more frequent over time, as more novel agents come to market and their efficacy is further elucidated.
A phase 2 study of trametinib for patients with pediatric glioma or plexiform neurofibroma with refractory tumor and activation of the MAPK/ERK pathway.
Authors: Perreault Sébastien , Sadat Kiaei Dorsa , Dehaes Mathieu , Larouche Valérie , Tabori Uri , Hawkin Cynthia , Lippé Sarah , Ellezam Benjamin , Cantin Edith , Routhier Marie-Ève , Caru Maxime , Vairy Stephanie , Legault Geneviève , Bouffet Eric , Ramaswamy Vijay , Coltin Hallie , Lafay-Cousin Lucie , Hukin Juliette , Erker Craig , Jabado Nada ,   TRAM-01 Study Team
Published: June 2022

2042 Background: Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children and the majority of PLGG have activation of the MAPK/ERK pathway. Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PLGG and PN, but no clinical trial has reported its efficacy. Methods: This multicenter phase II trial includes patients aged ≥ 1 month to ≤ 25 years with progressing/refractory PLGG groups or PN. The primary objective was to evaluate the overall response rate after daily oral trametinib administration for eighteen 28-day cycles. Results: As of January 31st, 2022, 60 patients with PLGG and 45 patients with PN have been enrolled. Median age is 9.5 years (range 1.8-25.4) for PLGG and 11 years (range 0.7-19.8) for PN. Median follow-up is 18 months (range 0.1-38.1). Fifty-three patients with PLGG were evaluable. The overall response includes: 1 complete response (CR) (1.9%), 7 partial response PR (13.2%), 17 minor response MR (32.1%), 23 stable disease (SD) (43.4%) and 5 progressive disease (PD) (9.4%). Twenty-eight patients with a total of 32 PN were available for volumetric analysis. Volumetric assessment demonstrated an overall response rate of 60.7% compared to 24.1% when using RECIST 1.1 and 62.5% of PN showed a decrease of more than 20% in volume. Median volume change was a decrease of 30% (range -93.5 to 14.3). A total of 59 (69.4%) patients discontinued treatment as planned after 18 cycles and 9 (10.6%) patients had to stop trametinib due to adverse events. Conclusions: Response rates observed in our study suggest that trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG and PN. Treatment was overall well tolerated. This trial will continue to gather data on duration of response and long-term outcome for PLGG and PN treated with trametinib. Clinical trial information: NCT03363217.
Prognostic significance of therapy-induced myelosuppression in newly diagnosed glioblastoma.
Authors: Weller Michael , Oppong Felix Boakye , Vanlancker Maureen , Stupp Roger , Nabors Louis B. , Chinot Olivier L. , Wick Wolfgang , Preusser Matthias , Gorlia Thierry , Le Rhun Emilie 
Published: June 2022

2055 Background: Myelosuppression is the major toxicity encountered during temozolomide chemoradiotherapy for newly diagnosed glioblastoma. Methods: We assessed the association of myelosuppression (neutropenia, thrombocytopenia, anemia, lymphopenia) during temozolomide chemoradiotherapy alone or in combination with experimental agents with progression-free survival (PFS) or overall survival (OS) in 2073 patients with newly diagnosed glioblastoma enrolled into five clinical trials: CENTRIC, CORE, EORTC 26082, AVAglio, and EORTC 26981. A landmark analysis approached was used. For each primary association analysis, a significance level of 1.7% was used. Results: Lower neutrophil counts at baseline were associated with better PFS (p = 0.011) and OS (p < 0.001), independently of steroid intake. Females experienced uniformly more myelotoxicity than males. Lymphopenia during concomitant chemoradiotherapy was associated with OS (p = 0.009): low-grade (1-2) lymphopenia might be associated with superior OS (HR 0.78, 98.3% CI 0.58-1.06) whereas high-grade (3-4) lymphopenia might be associated with inferior OS (HR 1.08, 98.3% CI 0.75-1.54). There were no associations of altered hematological parameters during concomitant chemoradiotherapy with PFS. During maintenance chemoradiotherapy, no significant association was found between any parameter of myelosuppression and PFS or OS, although exploratory analysis at 5% significance level indicated that either mild-to-moderate (HR 0.76, 95% CI 0.62-0.93) or high-grade lymphopenia (HR 0.65, 95% CI 0.46-0.92) were associated with superior OS (p = 0.013), but not PFS. Conclusions: The association of higher neutrophil counts at baseline with inferior PFS and OS requires further prospective evaluation. The link of therapy-induced lymphopenia to better outcome may guide the design for immunotherapy trials in newly diagnosed glioblastoma.
Phase 1 trial of ruxolitinib, temozolomide, and radiation in high-grade gliomas.
Authors: Ahluwalia Manmeet Singh , Rauf Yasmeen , Stevens Glen , Peereboom David M. 
Published: June 2022

2061 Background: Ruxolitinib is a novel, selective inhibitor of JAK1 (Janus kinase 1) and JAK2 and JAK3. JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus leading to modulation of gene expression. Dysregulation of the JAK/STAT pathway has been associated with several types of cancer and increased proliferation and survival of malignant cells. Preclinical evidence supports inhibition of JAJK STAT pathway arrogated glioma growth. Methods: Ruxolitinib is a novel, selective inhibitor of JAK1 (Janus kinase 1) and JAK2 and JAK3. JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, activation, and subsequent localization of STATs to the nucleus leading to modulation of gene expression. Dysregulation of the JAK/STAT pathway has been associated with several types of cancer and increased proliferation and survival of malignant cells. Preclinical evidence supports inhibition of JAJK STAT pathway arrogated glioma growth. Results: 60 patients were treated on the study and there were no dose limiting toxicity seen on the protocol. Survival data was calculated for GBM. The OS for arm 1 was 18.17 (10.15, NA) and was not reached for arm 2. The 1 year OS was 0.62 for arm 1 and 0.93 for arm 2. Patients that received ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks (Arm 2) had significantly better PFS and OS than those that received ruxolitinib + radiation x 60 Gy alone. Conclusions: Dose of 20 mg twice daily of ruxolitinib is safe with radiation and temozolomide. Preliminary survival data appears promising compared to the historical benchmarks and randomized phase 2 trial is planned. Clinical trial information: NCT03514069. [Table: see text]
Characterizing malignant transformation in patients with IDH-mutant glioma.
Authors: Liu Vicki , Eldred Blaine S.C. , Wetzel Ethan , Zapanta Rinonos Serendipity , Khanlou Negar , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy Francis , Ellingson Benjamin M. , Lai Albert 
Published: June 2022

2065 Background: Gliomas, which constitute the majority of primary brain cancers in adults, are assigned to a particular grade based on histological and molecular criteria set forth by the World Health Organization (WHO). A subset of initially low grade glioma patients transition to a higher grade at recurrence through a process known as malignant transformation (MT). Despite its significant implications on clinical prognosis, MT remains a poorly understood phenomenon in regards to its incidence rates, effects on survival, and potential prognostic factors. Our study aims to elucidate MT in patients that possess a mutation in the isocitrate dehydrogenase ( IDH) gene, one of the most common genetic alterations in gliomas. Methods: All known IDH mutant glioma patients, seen at UCLA between 1986 and 2022, who received at least 1 repeat resection for presumed recurrent disease were included. Based on surgical pathology reports, patients were categorized into MT and non-transforming progression groups, and further stratified by diagnosis in compliance with the 2016 WHO Classification of Tumors of the Central Nervous System. Relevant clinical information, including patient demographics, survival data, tumor microscopic descriptions, and magnetic resonance imaging, was accessed via electronic medical records. Kaplan Meier analyses were conducted to evaluate the predictive power of various clinical, pathological, and radiological markers. Results: Of 724 total IDH mutant patients screened, 253 received a second surgery and were thus incorporated in this study. Among the 196 patients with lower grade pathologies capable of MT, 129 (65.8%) progressed to a higher grade at recurrence while 71 (36.2%) did not. By diagnosis, the incidence rates of MT for initial grade 2 astrocytomas, grade 3 astrocytomas, and grade 2 oligodendrogliomas were determined to be 74.7%, 48.9%, and 66.1%, respectively. MT was associated with worse overall survival and post-recurrence survival compared to non-transformation in astrocytomas, a trend not seen in oligodendrogliomas. Across all relevant diagnoses, a subset of 36 MT patients did not receive treatment in the interval between initial and recurrent surgery, demonstrating the existence of spontaneously occurring MT. Furthermore, consolidating data from pathology and MRI reports revealed that a greater extent of abnormal molecular characteristics at initial diagnosis and earlier post-operative contrast enhancement may predict MT. Conclusions: These results highlight the distinct nature of gliomas that undergo MT, particularly in tumors of astrocytic differentiation. Considering its adverse impact on clinical outcome, understanding and anticipating this phenomenon is instrumental for the determination of optimal treatment among glioma patients.
Spatiotemporal multiomic landscape of human medulloblastoma at single cell resolution.
Authors: Liu Hailong , Jiang Tao , Qiu Xiaoguang 
Published: June 2022

2069 Background: Medulloblastoma is the most common malignant childhood tumor type with distinct molecular subgroups. While advances in the comprehensive treatment have been made, the mortality in the high-risk group is still very high, driven by an incomplete understanding of cellular diversity. Methods: We use single-nucleus RNA expression, chromatin accessibility and spatial transcriptomic profiling to generate an integrative multi-omic map in 40 human medulloblastomas spanning all molecular subgroups and human postnatal cerebella, which is supplemented by the bulk whole genome and RNA sequences across 300 cases. Results: This approach provides spatially resolved insights into the medulloblastoma and cerebellum transcriptome and epigenome with identification of distinct cell-type in the tumor microenvironment. Medulloblastoma exhibited three tumor subpopulations including the quiescent, the differentiated, and a stem-like (proliferating) population unique to cancer, which localized to an immunosuppressive-vascular niche. We identified and validated mechanisms of stem-like to differentiated process among the malignant cells that drive tumor progression. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing stem-like malignant cells as a hub for intercellular communication. Multiple features of potential immunosuppression and angiogenesis were observed, including Treg cells and endothelial cells co-localization in compartmentalized tumor stroma. Conclusions: Our study provides an integrative molecular landscape of human medulloblastoma and represents a reference to advance mechanistic and therapeutic studies of pediatric neuro-oncological disease.
Customized autoantibodies (autoAbs) profiling to predict and monitor immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI).
Authors: Genta Sofia , Keshavarzi Sareh , Yee Noelle , Heirali Alya , Hansen Aaron Richard , Siu Lillian L. , Saibil Samuel , Stayner Lee-Anne , Yanekina Maryia , Sauder Maxwell , Salawu Abdulazeez , Spiliopoulou Pavlina , Vornicova Olga , Vilbert Maysa Tamara Silveira , Butler Marcus O. , Bedard Philippe L. , Abdul Razak Albiruni Ryan , Coburn Bryan , Chruscinski Andrzej , Spreafico Anna 
Published: June 2022

2528 Background: Using a customized microarray, we previously reported that patients (pts) who develop irAEs grade (G)≥2 and those who do not, have different median fluorescent intensity (MFI) levels of specific autoAbs at baseline (pre-ICI). Leveraging a larger dataset, we evaluated whether overall baseline autoAbs elevation and early increases in autoAbs after ICI can predict irAEs as well as if steroid treatment can reduce autoAbs. Methods: Plasma was obtained from pts receiving ICI in two clinical trials (MET4-IO, NCT03686202 and INSPIRE, NCT02644369) and from healthy controls (hc). Collection time points in MET4-IO and INSPIRE studies included: baseline, 3-4 weeks (w), 6-8 w, 24 w and at the end of treatment and baseline and 6 w respectively. Arrays with 162 autoAg customized for frequent irAEs were incubated with plasma and probed with Abs to detect IgG and IgM reactivity. AutoAbs with MFI >500 per individual were compared between hc and pts with and without irAEs G≥2 by the Student-t test. Results: Samples from 114 pts and 14 hc were analyzed (pts characteristics are summarized in the Table). G≥2 irAEs included: hypothyroidism (13), pneumonitis (10), colitis (7), hepatitis (4), skin toxicity (7), infusion reaction (2), pancreatitis (2), meningitis (1), hypophysitis (1), corneal ulcer (1), high creatinine (1), myocarditis (1), myositis (1), diabetes (1), mucositis (1), myasthenia (1) and adrenal failure (1). Hc had less autoAbs with MFI >500 as compared to pts at baseline (median 32 vs 62 p<0.001). IgG with MFI >500 were higher at baseline in pts who developed G≥2 irAEs vs those without G≥2 irAEs (median 39 vs 33, p=0.03). In 23 pts with plasma collected at the time of irAEs, we observed a significant increase of autoAbs with MFI>500 from baseline (median 84 vs 77 p= 0.009). Paired samples at the time of irAEs and after steroids were available for 9/23 pts, showing lower autoAbs after steroid treatment (54 vs 79 p=0.006). No differences in autoAbs with MFI>500 pre and post ICI were seen in pts without G≥2 irAEs (baseline vs first post ICI collection median 58 vs 60, p=0.13). Conclusions: We observed a higher number of IgG with MFI >500 at baseline and a greater increase after ICI administration in individuals with irAEs compared to those without irAEs. Steroid treatment resulted in a decrease in autoAbs. A prospective study is ongoing to validate the potential role of autoAbs for risk stratification and monitoring of irAEs. [Table: see text]