bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing virtual mind-body programming to support cancer patients during COVID-19.
Authors: Mao Jun J. J. , Hung Kin Wai (Tony) , Emard Nicholas , Polubriaginof Fernanda C. G. , Lynch Kathleen , Atkinson Thomas Michael , Trevino Kelly Marie , Jensen Claus 
Published: June 2021

1585 Background: Despite growing evidence of mind-body therapies for physical and psychological health among patients with cancer, their access remains limited. The COVID-19 pandemic has further disrupted the delivery of necessary cancer and supportive care; thus, the need to support patients with cancer is unprecedented. To expand the reach and access of mind-body therapies, we developed, implemented, and evaluated a novel virtual mind-body program for patients with cancer. Methods: We rapidly developed a 7-day a week virtual mind-body program, Integrative Medicine at Home (IM@Home), for patients with cancer (ages ≥18 years) and deployed it on April 1st, 2020. IM@Home included mind-body group therapy classes in fitness, meditation, yoga, dance, tai chi, and music delivered using Zoom video conferencing. Classes ranged from 30-45 minutes and were led by an integrative medicine clinician. Patients had the option to register for a 1-month, 3-month, or 6-month membership to gain unlimited access to all virtual mind-body classes. Multi-method evaluation was conducted using the RE-AIM conceptual framework to guide surveys and qualitative interviews. Surveys were analyzed using descriptive statistics and interviews were analyzed using grounded theory. Results: Between April 2020 and January 2021, IM@Home registered over 32,000 class participants, with a weekly average attendance of 700-800 participants. In a 4-month post-deployment survey (n = 131), nearly all participants were satisfied with IM@Home (93.9%) and would recommend the program to friends and family (95.4%). A majority of participants also found IM@Home to be simple to use (87.0%) and said the program had a variety of classes that interested them (93.1%). Three-quarters of participants (74.8%) were taking 3 to 7 classes a week (range: 1 to 15 classes), among which the most popular classes were fitness (88.7%), chair yoga (37.1%), and tai chi (33.1%). Most participants preferred a 3-month membership (51.6%), followed by a 6-month membership (19.5%). In qualitative interviews (n = 30), participants reported IM@Home helped them to: 1) maintain structured routines and stay motivated to exercise; 2) cope with COVID-19-related and cancer-related stressors; and 3) connect with their fellow cancer patient community and foster social relationships during a time of isolation. Conclusions: Virtual mind-body programming, through IM@Home, reached many patients with cancer to address their physical and psychological challenges during COVID-19. As patients with cancer experience high physical and psychological symptom burden following diagnosis, future clinical trials are needed to evaluate the specific effects of IM@Home when integrated into active treatment and survivorship care.
ALK inhibitors for treatment of adult-onset neuroblastoma.
Authors: Stiefel Jessica , Kushner Brian H. , Basu Ellen M. , Roberts Stephen S. , Modak Shakeel 
Published: June 2021

2001 Background: Neuroblastoma (NB), a rare malignancy of the sympathetic nervous system, is a tumor of early childhood with > 90% of cases diagnosed before 5 years of age. Adult-onset NB (AON) is extremely rare and differs significantly from childhood disease. AON, while more indolent, is usually metastatic at diagnosis, generally chemotherapy-resistant, and almost invariably lethal. Additionally, standard therapies for NB such as dose-intensive chemotherapy and anti-GD2 antibody are poorly tolerated by adults. Prior studies have shown AON is enriched for genomic aberrations especially ALK (Suzuki et al 2018). Although ALK inhibitors (ALKi) are effective for therapy of lymphoma and non-small cell lung cancer, their use in AON has not previously been reported. Methods: Retrospective review of patients > 18 years old at diagnosis seen at Memorial Sloan Kettering Cancer Center (MSKCC) was performed after IRB approval. Response to ALKi was evaluated using International Neuroblastoma Response Criteria; objective responses were also noted. Progression-free (PFS) and overall survival (OS) was calculated using Kaplan-Meier methods. Results: Since 1979, 52 patients with AON were seen at MSKCC. Of 23 patients evaluated, 14 (61%), harbored somatic ALK mutations. Seven were treated with FDA-approved ALKi. One patient initially diagnosed at 12 years of age was treated with ALKi following a relapse 15 years later. Overall, all ALKi were well-tolerated; reported adverse events included grade 1-2 nausea and vomiting (n = 6), and neurologic symptoms including hallucinations, drowsiness, and dizziness (n = 1 patient each) which resolved after stopping ALKi. Four patients received > 1 ALKi either due to progressive disease or intolerance. Most patients responded to the first ALKi with objective though partial response (n = 5) while one had progressive disease (PD). Median time to progression for initial ALKi was 15.5 months (10-45). One patient with no evaluable disease after four prior relapses was treated with alectinib for 36 months without PD. Of the patients treated with a second ALKi (n = 4), 1 had CR and 2 had PR after not having progressed previously, while the other had stable disease. Median OS from beginning treatment with first ALKi was 46.5 (17-74) months. Conclusions: AON is a rare disease which is a therapeutic challenge. Enrichment of ALK mutations permits consideration of targeted therapy. ALKi were well tolerated, often associated with significant responses, and treatment with serial ALKi led to ongoing benefit. Given this, ALKi should be considered for treatment in future AON cases.
Targeted agents recommended by the CNS TAP tool compared to those selected by a tumor board in a molecularly-driven clinical trial in children and young adults with DIPG.
Authors: Roberts Holly , Ravi Karthik , Kline Cassie , Mueller Sabine , Koschmann Carl Johannes , Marini Bernard , Franson Andrea 
Published: June 2021

2048 Background: Genetic sequencing of diffuse intrinsic pontine glioma (DIPG) and diffuse midline glioma (DMG) biopsy specimens has revealed genomic heterogeneity, fueling an interest in individualized, targeted treatment options. The Pacific Pediatric Neuro-Oncology Consortium recently completed a feasibility study PNOC003: Molecular Profiling for Individualized Treatment Plan for DIPG (NCT02274987), in which a multidisciplinary tumor board recommended targeted agents based on the molecular and genetic profiling of each patient’s tumor. Separately, our group developed a numeric scoring tool of targeted anticancer agents, the Central Nervous System Targeted Agent Prediction (CNS TAP) tool, which combines pre-clinical, clinical, and CNS penetration data with patient-specific genomic information to generate a numeric score for each agent to objectively evaluate these targeted therapies for use in patients with CNS tumors. We hypothesized that highly-scored agents within the CNS-TAP tool would overlap, at least in part, with the agents recommended by the molecular tumor board in PNOC003. Methods: For each study participant (n=28), a retrospective analysis was completed, utilizing the genomic report to identify actionable genetic alterations and to input patient-specific data into CNS TAP to identify the highest scoring agents. We compared high-scoring agents within the CNS TAP tool with recommendations from the PNOC003 tumor board for each of the enrolled 28 patients. Results: Overall, 93% (26/28) of patients had at least one agent recommended by both the tumor board and CNS TAP. Additionally, 39% (37/95) of all agents recommended by the tumor board were also selected by CNS TAP, with additional analysis ongoing. Conclusions: There was significant overlap between the highest-scoring and selected agents via CNS TAP compared with those chose by the molecular tumor board. Through this work, we also identified factors that likely contributed to the discordance in choice of targeted therapies. Without clinician input, the CNS TAP tool is unable to account for drug-drug interactions, includes only designated anticancer agents, and cannot easily be updated in real time, requiring extensive manual literature review for each included agent. However, CNS TAP provides an objective evaluation of targeted therapies, in contrast to inherently subjective recommendations of a tumor board. Given the discordance identified between these methods and the strengths of each, a prospective study incorporating both CNS TAP and a molecular tumor board for targeted therapy selection in patients with high grade glioma is warranted.
Scalp-sparing radiation with concurrent temozolomide and tumor treating fields (SPARE) for patients with newly diagnosed glioblastoma.
Authors: Miller Ryan C , Song Andrew Jehyun , Ali Ayesha , Bar-Ad Voichita C , Martinez Nina Leyson , Glass Jon , Alnahhas Iyad , Andrews David W. , Judy Kevin , Evans James J , Farrell Christopher , Werner-Wasik Maria , Chervoneva Inna , Ly Michele , Palmer Joshua David , Liu Haisong , Shi Wenyin 
Published: June 2021

2056 Background: Standard of care for patients with newly diagnosed glioblastoma includes concurrent chemoradiation and maintenance temozolomide with Tumor Treating Fields (TTFields). Preclinical studies suggest TTFields and radiation treatment have synergistic effects. We report our clinical trial evaluating safety and tolerability of scalp-sparing radiation with concurrent temozolomide and TTFields. Methods: This is a single arm pilot study. Adult patients (age ≥ 18 years) with newly diagnosed glioblastoma and a KPS of ≥ 60 were eligible. All patients received concurrent scalp-sparing radiation (60 Gy in 30 fractions) with temozolomide (75 mg/m2 daily) and TTFields (200 kHz). Maintenance therapy included temozolomide and continuation of TTFields. Radiation treatment was delivered through TTFields arrays. The primary endpoint was safety and toxicity of TTFields concurrent with chemoradiation in patients with newly diagnosed glioblastoma. Results: A total of 30 patients were enrolled in the trial. Twenty were male and ten were female, with a median age of 58 years (range 19 to 77 years). Median KPS was 90 (range 70 to 100). Median follow-up was 8.9 months (range 1.6 to 21.4 months). Twenty (66.7%) patients had unmethylated MGMT promotor status and ten (33.3%) patients had methylated promoter status. Median time from surgery to radiation was 34 days (26 to 49 days). Scalp dose constraints were achieved for all patients, with the mean dose having a median value of 8.3 Gy (range 4.3 to 14.8 Gy), the D20cc median was 26.1 Gy (range 17.7 to 42.8 Gy), and the D30cc median was 23.5 Gy (range 14.8 to 35.4 Gy). Skin adverse events (AEs; erythema, dermatitis, irritation, folliculitis) were noted in 83.3% of patients, however, these were limited to Grade 1 or 2 events, which resolved spontaneously or with topical medications. No patient had radiation treatment interruption due to skin AEs. Other Grade 1 events included pruritus (33.3%), fatigue (30%), nausea (13.3%), headache (10%), dizziness (6.7%), and cognitive impairment (3.3%). Other Grade 2 events included headache (3.3%). Nineteen patients (63.3%) had progression, with a median PFS of 7.6 months (range 1.6 to 12.7 months). Overall survival was not reached. Conclusions: Concurrent TTFields (200 kHz) with scalp-sparing chemoradiation is a safe and feasible treatment option with limited toxicity. Future randomized prospective trials are warranted to define therapeutic advantages of concurrent TTFields with chemoradiation. Clinical trial information: NCT03477110.
A single-arm phase Ib study of autologous cytokine-induced killer (CIK) cell immunotherapy in combination with sintilimab plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)-CCICC-002.
Authors: Ren Xiubao , Zhou Li 
Published: June 2021

2531 Background: Immune checkpoint inhibitors plus chemotherapy had showed benefits for advanced non–small-cell lung cancer (NSCLC) patients without targetable mutations. Autologous cytokine-induced killer (CIK) cells can restore the antitumor immunity to improve patient outcome. Combining CIK cells with anti-PD-1 mAb plus chemotherapy may strengthen the results in patients with advanced NSCLC. Methods: This is a single-center, open-label, phase 1b trial of combination CIK cells with sintilimab (anti-PD-1 mAb) plus chemotherapy in stage IIIB-IV NSCLC patients. Systemic therapy naïve patients received platinum-based doublet chemotherapy, sintilimab, and CIK cells every 3 weeks for 4 cycles，then sintilimab, and CIK cells for maintenance therapy until disease progression or unacceptable toxicity. Results: From May 2019 to Jan 2021, 34 patients (19 squamous， 15 non-squamous NCSLC)aged 46-73 years (median age 64 years) were enrolled. Among 32 evaluable patients, the ORR was 81.3% (73.7% in squamous and 92.3% in non-squamous NSCLC)and DCR was 100%. Among the 25 PR assessed by RECIST, CMR was demonstrated in 5 (23.1%) by PET-CT. Among 3 patients with brain metastases, 2 patients achieve intracranial CR, and 1 was PR. With a median follow-up of 7.5 months, the median DOR was not reached (range 0.5m-NA), and the median PFS and OS were not mature. Grade 3 or more TRAEs included pneumonia (n = 3); thrombocytopenia, leukopenia (n = 2 each); anemia, dysphagia, cardiomyopathy, rash (n = 1 each). Biomarkers and subgroups which correlated with efficacy and AEs are being analyzed included TMB, PDL1 expression, distribution of TILs, cytokines and so on. Conclusions: CIK cells therapy in combination with sintilimab plus chemotherapy were well tolerated and showed encouraging efficacy. Further studies are warranted to confirm these preliminary results. Research Sponsor: Tianjin Medical University Cancer Institute and Hospital. Clinical trial information: NCT03987867. [Table: see text]
GS-3583, a novel FLT3 agonist Fc fusion protein, to expand conventional dendritic cells in healthy volunteers.
Authors: Rajakumaraswamy Nishanthan , Dauki Anees , Kuhne Michelle R. , Trowe Torsten , He Jing , Clarke Christopher , Carr Brian , Worth Angela , Vashishtha Anshu , Schwabe Christian , Othman Ahmed A. 
Published: June 2021

2559 Background: Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T cells and their recruitment to tumor microenvironment (TME). However, cDC1s are often underrepresented in the TME. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L), a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to expansion of cDC1s in the periphery which can then be recruited into the TME. We hypothesize that FLT3 pathway stimulation using GS-3583, a FLT3 agonist Fc fusion protein, has the potential to promote T cell mediated anti-tumor activity. Methods: This was a first-in-human placebo-controlled study of GS-3583 in healthy volunteers to evaluate the safety, PK, and PD of escalating single doses (ranging from 75μg to 2000μg) of GS-3583. The study was blinded to the subjects and the investigator. Each dose cohort enrolled 8-12 healthy subjects who received GS-3583 or placebo as single IV infusion at 3:1 ratio. Subjects were observed in the phase 1 unit for 15 days and then for 12 weeks as outpatients. As part of the PD evaluation, we investigated the changes in the number of cDC1s and cDC subtype 2 (cDC2) cells. Results: As of 8th Feb 2021, selected safety, PK and PD data from the first 3 cohorts were available. GS-3583 was well tolerated and all subjects had been discharged. To date, there have been no serious or grade 3 or higher adverse events. Preliminary PK analysis suggested dose-dependent increase in GS-3583 exposure (AUC and Cmax). Preliminary PD analysis shows that administration of GS-3583 resulted in dose-dependent increases in cDC1/cDC2 cells that peaked at day 5 or day 8 and returned to baseline within three weeks of drug administration. Conclusions: GS-3583 was safe and well tolerated and induced dose dependent expansion of dendritic cells in the periphery. In patients with cancer, this increase in dendritic cells can be utilized to enhance anti-tumor responses to immuno-oncology therapies.[Table: see text]
Pembrolizumab in microsatellite instability high (MSI-H)/mismatch repair deficient (dMMR) cancers: Updated analysis from phase 2 KEYNOTE-158 study.
Authors: Maio Michele , Ascierto Paolo Antonio , Manzyuk Ludmila , Motola-Kuba Daniel , Penel Nicolas , Cassier Philippe A. , Bariani Giovanni , De Jesus-Acosta Ana , Doi Toshihiko , Longo Federico , Miller Wilson H. , Oh Do-Youn , Gottfried Maya , Wang Ruixue , Jin Fan , Norwood Kevin Glen , Marabelle Aurelien 
Published: June 2021

2565 Background: Approval of pembrolizumab for the treatment of unresectable or metastatic MSI-H/dMMR solid tumors that have progressed on prior therapy was supported by data from KEYNOTE-158 (NCT02628067). At the data cutoff of Dec 6, 2018, the ORR was 34.3% among 233 patients (pts) with MSI-H/dMMR solid tumors enrolled in all cohorts of KEYNOTE-158, 77.6% had duration of response (DOR) ≥24 mo, median PFS was 4.1 mo, and median OS was 23.5 mo. We present results from 351 pts enrolled in KEYNOTE-158 cohort K at the data cutoff of Oct 5, 2020. Methods: Cohort K of this phase 2, open-label study enrolled adults with any previously treated advanced noncolorectal MSI-H solid tumor, measurable disease per RECIST v1.1, and ECOG PS of 0–1. MSI-H/dMMR status was assessed locally from a tumor tissue sample and defined as ≥1 of 4 MMR proteins absent by immunohistochemistry or as ≥2 allelic loci size shifts of 5 microsatellite markers by PCR. Pts received pembrolizumab 200 mg Q3W for up to 35 cycles or until PD, unacceptable toxicity, investigator decision, or withdrawal of consent. The primary endpoint was ORR per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints were DOR and PFS per RECIST v1.1 by BICR, OS, and safety. Efficacy was assessed in all pts who received ≥1 dose of treatment with ≥6 mo follow-up; safety was assessed in all treated pts. Results: 351 pts were enrolled in KEYNOTE-158 cohort K across multiple tumor types, including endometrial (22.5%), gastric (14.5%), small intestine (7.4%), ovarian (7.1%), cholangiocarcinoma (6.3%), and pancreatic (6.3%). 41.0% had 1 prior line of therapy; 55.6% had ≥2 prior lines. Median time from first dose to database cutoff (Oct 5, 2020) was 37.5 (range, 0.2–55.6) mo; 16.0% were continuing treatment. The ORR among the 321 eligble pts was 30.8% (CR, 27; PR, 72); median DOR was 47.5 mo (Table). Treatment-related AEs occurred in 64.7% of pts (grade 3–5, 12.0%), led to discontinuation in 6.6%, and led to death in 3 pts (myocarditis, pneumonia, and Guillain-Barre syndrome). Immune-mediated AEs and infusion reactions occurred in 20.2% of pts (grade 3–4, 4.3%) and led to death in 2 pts with no other contributing factors (myocarditis [AE start, day 26; death, day 33] and Guillain-Barre syndrome [AE start, day 22; death, day 41]). Conclusions: Pembrolizumab demonstrated a high ORR (30.8%), durable clinical benefit, and a manageable safety profile in this heavily pretreated advanced MSI-H/dMMR noncolorectal pan-tumor population. Clinical trial information: NCT02628067. [Table: see text]
Phase I dose escalation of KD033, a PDL1-IL15 bispecific molecule, in advanced solid tumors.
Authors: Luke Jason J. , Olszanski Anthony J. , Puzanov Igor , Lu Dan , Hackett Adrian , Martomo Stella , Patel Jeegar , Schueller Olivier , Mora Alessandro , Schlitt Miranda , Li Linghui 
Published: June 2021

2568 Background: IL-2 and IL-15 signal through the shared IL-2/15 βγ receptor, but unlike IL-2, IL-15 does not expand regulatory T cells (Tregs), does not mediate activation-induced cell death and may have an improved therapeutic index. KD033 is a fusion antibody combining a fully human, high affinity anti-human Programmed Death Ligand 1 (PD-L1) IgG1 antibody with the human IL-15 receptor alpha (IL15Rα) sushi domain and human IL-15 (IL-15). KD033 (or its mouse cross reactive surrogate molecule, srKD033) has been extensively characterized in multiple in vitro and in vivo nonclinical studies. The fusion of anti-PD-L1 antibody to IL-15 significantly increases the maximal-tolerated dose (MTD) of srKD033 in mice compared to free IL-15. In addition, srKD033 has exhibited increased efficacy in rejecting tumors in mice as compared to the combination of its individual components, anti-PD-L1 antibody and IL-15. Methods: This is a phase 1, open-label, multiple ascending dose, multi-center clinical trial being conducted in patients with metastatic or locally advanced solid tumors (NCT04242147). The primary objective is to determine the safety and tolerability and the MTD of KD033. Secondary objectives include characterization of PK and immunogenicity, evaluation of CD8 T and NK cell activation and assessment of best overall response and duration of response. KD033 is administered by IV infusion over 30 minutes every 14 days. Accelerated intra-patient dose escalation across the initial three dose levels, followed by 3+3 escalation thereafter, is investigating dose ranges from 3 µg/kg to 600 µg/kg. Efficacy evaluation is planned in an expansion cohort of patients with PD-1/L1 refractory tumors. Results: A total of 7 patients have received treatment. Three patients were dosed in Cohort 1 and four patients were dosed in Cohort 2. Through two dose escalation cohorts (3 µg/kg – 25 µg/kg), no dose-limiting toxicities have been reported. Grade 1-2 treatment-related toxicities, when observed, resolved within 24 hours with supportive management. 6 patients are evaluable for treatment response with one patient (adenoid cystic carcinoma) in the first cohort having stable disease for more than 6 months. Conclusions: KD033 has been well tolerated early in dose escalation with on-mechanism pharmacodynamics consistent with IL-15 agonism. Clinical trial information: NCT04242147.