bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-based retrospective analysis of response assessment criteria in patients with glioblastoma.
Authors: Abbasian Parandoush , Ryner Lawrence , Lambert Pascal , Mann Anmol , Shankar Jai , Essig Marco , Pitz Marshall W. 
Published: June 2022

2041 Background: Patients with glioblastoma are often treated with radiation and chemotherapy following surgery. Disease recurrence often occurs early in the disease course and during initial therapy, yet assessment of treatment response with MRI is highly variable in some situations. We sought to describe the clinical and imaging assessment and outcomes of an unselected cohort of patients with glioblastoma following the publication of the Response Assessment in Neuro-Oncology criteria. Methods: Patients diagnosed with glioblastoma in Manitoba, Canada, from 2012-2018 were identified from the Manitoba Cancer Registry. Chart review was performed to identify treatments given and decisions made by the treating team, and imaging analysis was performed to assess based on RANO and mRANO criteria. Determination of progression versus pseudoprogression according to these criteria was performed using clinical decision-making and review of follow-up imaging for confirmation. At time of the response assessment visit, patients were assessed by a primary oncologist (Radiation or Medical) and were also discussed at multidisciplinary Case Conference (comprised of Medical and Radiation Oncology, Neurosurgery, Neuropathology, and Neuroradiology). Treatment decisions were made with patient and primary oncologist, guided by input from the Case Conference. Tumour measurements were performed both in 2D using Product of Perpendicular Diameter analysis (PPD) and 3D volumetric measurements with/without necrotic region. Overall Survival (OS) and Progression Free Survival (PFS) were estimated to evaluate the effectiveness of response assessments and Kaplan-Meier method was used to compare the time to progression resulted from RANO, mRANO, and clinical impression. Results: A total of 285 patients were identified with a pathological diagnosis of glioblastoma. Of those, 199 (35% male, 65% female) were treated with concurrent temozolomide and radiation (75% 60Gy and 25% < 60Gy), and more than 90% went on to receive adjuvant temozolomide. Median Overall Survival of the 199 was 13.2 months. Of those treated with concurrent therapy, 122 (61%) had MRI studies with equivocal results within the first 6 months, with confirmatory MRI showing true progression in 73 (59.8%), pseudoprogression in 45 (36.9%), and 4 patients with undetermined outcome. Formal RANO and mRANO comparison is ongoing. Conclusions: Response assessment for patients with glioblastoma remains a frequent challenge despite the use of MRI and established response criteria, with more than half of patients having equivocal imaging changes and a high frequency of pseudoprogression.
A single-institution, retrospective examination of new contrast enhancement, progression, and pseudoprogression in IDH mutant glioma.
Authors: Wetzel Ethan , Eldred Blaine S.C. , Liu Vicki , Zapanta Rinonos Serendipity , Khanlou Negar , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy Francis , Ellingson Benjamin M. , Lai Albert 
Published: June 2022

2043 Background: IDH mutant glioma patients are followed by MRI, where new contrast enhancement (CEnew) is a hallmark of tumor progression. Interpretation of CEnew is confounded by pseudoprogression (PsP), the appearance of CEnew that spontaneously resolves on subsequent scans. PsP has been characterized in IDH wildtype patients, but is poorly understood in the IDH mutant category. This study represents an examination of the characteristics and impacts on patient survival of CEnew in IDH mutant gliomas. Methods: Of the 724 confirmed IDH mutant glioma patients treated at UCLA between 1998 and 2022, 587 were included (median follow-up = 5.23 years). Patients were excluded based on these criteria: <4 MRI scans, unknown IDH status, and unknown WHO 2016 diagnosis. CEnew was first identified by direct review of images and confirmed by the radiology report. Any new enhancement appearing on the first post surgical MRI was not considered CEnew. CEnew was interpreted as progression after surgical resection indicating tumor or the re-initiation of chemotherapy or radiation and was considered PsP after the resolution of enhancement without new treatment initiation. Some PsP patients could have received bevacizumab. Kaplan-Meier survival analyses were used to examine overall survival differences between groups. Results: 327 of 587 patients developed CEnew. The incidence of CEnew was higher in Grade 4 Astrocytoma (G4 Astro) versus all other pathologies and lowest in LO (p < 0.05). The Enhancement Free Survival (EFS) was shortest for G4 Astro patients (p =.002); LO patients had the longest median EFS of 2602 days (p = 0.002). The development of CEnew and presence of preoperative enhancement were both found to be negative survival prognosticators in all pathologies (p < 0.05). From our analysis, 92 patients developed PsP and 177 developed progression. The median duration of a PsP spot was 244 days. PsP spots appeared earlier than progression spots (median 538 vs 1113 days, p =.001). The incidence of PsP was highest in the G4 Astro group and lowest in LO patients. Survival analysis of patients with progression versus those with PsP and progression shows PsP is associated with longer OS in the entire cohort and the LO, AO, AA, and G4 Astro groups (p < 0.05). 100% of PsP patients received radiation therapy (RT). The median time from the end of RT to PsP was 209 days. Conclusions: While CEnew in IDH mutant gliomas is associated with reduced OS, poorer outcome is driven by progressors. PsP represents 28% of CEnew instances, typically occurs within 1 year of RT and have superior outcome to progressors and equivalent to of patients that do not display CEnew. [Table: see text]
Indirect assessment of tumor-infiltrating lymphocyte activity in serum for predicting outcome in patients with glioblastoma treated with immunotherapy in the recurrent setting.
Authors: Jensen Christina , Maarup Simone Bendix , Poulsen Hans Skovgaard , Hasselbalch Benedikte , Karsdal Morten A. , Svane Inge Marie , Lassen Ulrik Niels , Willumsen Nicholas 
Published: June 2022

2059 Background: Glioblastoma (GBM) is an aggressive brain tumor and despite efforts in developing new effective therapies, patient survival remains low. There is increasing interest in using immune checkpoint inhibitors (ICIs) for GBM, however the immunosuppressive (cold tumor) characteristics of GBM limit the efficacy of ICIs. Consequently, there is a need to identify patients with active tumor-infiltrating lymphocytes (hot tumor). Several studies have shown that brain extracellular matrix such as type IV collagen has a dynamic composition with protease-induced alterations. In this study, we evaluated the clinical utility of a non-invasive biomarker of granzyme B degraded type IV collagen (C4G) reflecting tumor-infiltrating lymphocyte activity and of matrix metalloproteinase (MMP) degraded type IV collagen (C4M) in GBM patients treated with nivolumab (anti-PD-1) and bevacizumab (anti-VEGF) in the recurrent setting. Methods: C4G and C4M were measured in serum from 22 controls and 39 GBM patients previously treated with surgery, radiotherapy and chemotherapy in the primary setting. After GBM recurrence, 18 patients underwent salvage resection (arm A) however 21 patients had no possibility for resection (arm B). All patients were treated with nivolumab and bevacizumab (NCT03890952 phase II study). Baseline GBM samples were taken before the second-line treatment. The association between C4G levels and outcome was evaluated by Cox regression analysis for overall survival (OS) and odds ratio (OR) calculations for complete response (CR) rate after dichotomizing patients into low vs high levels of C4G (median cutpoint). Results: C4G (p = 0.004), but not C4M (p = 0.166), was significantly elevated in serum from GBM patients compared to controls. Moreover, patients with high C4G levels had a significantly increased likelihood of experiencing CR (OR=6.68, p<0.0001). Furthermore, patients with high C4G experienced improved OS compared to low C4G (HR=0.39), and this remained significant after adjusting for other significant risk factors (treatment arm and MGMT methylation) by multivariate analysis (HR=0.44) (table). Conclusions: A non-invasive biomarker reflecting tumor-infiltrating lymphocyte activity (C4G) has the potential to identify GBM patients responding to nivolumab and bevacizumab in the recurrent setting. In the future, this may provide a non-invasive biomarker tool for stratifying patients with GBM for ICI trials. Clinical trial information: NCT03890952. [Table: see text]
Treatment patterns of patients with glioblastoma multiforme in the real-world setting in a developing country.
Authors: Sánchez Hernández Juan José , Zarroca Palacio Santiago , Trejo Rosales Raul Rogelio , Remolina Bonilla Yuly Andrea , De Jesus Hernandez Dulce Angelica , Najar Miriam , Lizcano Aguilar Nestor Javier , Hernandez Castillo Marco Antonio , Cruz Andrea , Vélez Martínez Amairany Guadalupe , Sanchez Eduardo , Morales Hernández Karina , Irigoyen Álvarez Angel Gabriel Ignacio 
Published: June 2022

2067 Background: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor. Surgery followed of temozolomide administered concurrently with radiation therapy (RT) and followed by adjuvant temozolomide for six cycles significantly improved survival compared with radiation therapy alone in a randomized controlled trial published by Stupp and colleagues. Real world evidence in patients with GBM is scarce in Latin America. Methods: A retrospective study was conducted at the Hospital de Oncología, Centro Médico Nacional Siglo XXI, a referral center in Mexico City. We included histologically confirmed patients with GBM treated in a period from January 2015 to January 2019. Descriptive statistics and Kaplan-Meier method with log-rank were used for analysis. Cox regression was used for multivariate analysis. Results: A total of 184 patients were included, 96 were men (52,2%) and 88 were women (47.8%); median age was 56 years (range 18 - 87). ECOG performance status scale 0-1, and ≥ 2 represented 34.2% and 65.8% of the cohort, respectively. Maximal surgical resection was performed in 172 patients (93%). After surgery or biopsy, 12 patients (6.5%) did not receive any subsequent oncology treatment. Treatment with concomitant RT with TMZ was offered to 156 patients (84.4%) and RT alone to 16 patients (8.7%). The most common RT modality was conventional fractionation (60 Gy in 30 fractions) in 75% of cases. After concurrent therapy, 135 (86.5%) received adjuvant TMZ, of which 53.4% received ≤ 5 cycles and 46.6% received ≥ 6 cycles. The median overall survival of the entire cohort was 20.1 months (95% CI 13.3 - 26.9 months). Survival in patients with adjuvant TMZ was superior versus patients who did not receive complete multimodal treatment (26.3 months vs 10.5 months, p < 0.001). In the multivariate analysis, adjuvant chemotherapy was the only independent factor with statistical significance HR 0.18 (95% CI, 0.08 to 0.41 [p < 0.001]). Conclusions: In this retrospective study our data confirm that receiving adjuvant TMZ treatment is beneficial in prolonging overall survival compared to those who do not receive adjuvant therapy in patients with GBM.
The interim result of a phase I/II study of nivolumab with or without ipilimumab in combination with multi-fraction stereotactic radiosurgery for recurrent, high-grade, radiation-relapsed meningioma.
Authors: Huang Jiayi , Gao Feng , Shimony Joshua , Johanns Tanner Michael , Mantica Megan , Gershon Timothy Robin , Ney Douglas Edward , Tuncer Tolga , Mendez Joe Sammy , Streicher Howard , Campian Jian Li 
Published: June 2022

2068 Background: There is a lack of effective therapy for recurrent high-grade meningiomas who relapsed after prior radiation therapy (RT). ETCTN 10186 is a phase I/II study to evaluate the feasibility and preliminary clinical efficacy of combining reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab for recurrent high-grade meningiomas. The preliminary results from the phase I portion are reported here. Methods: Recurrent grade II-III meningioma patients were treated with radiosurgery plus nivolumab with or without ipilimumab. Key eligibility criteria include age ≥ 18 years; ECOG score ≤ 2; tumor diameter 1-5 cm; prior radiation dose ≤ 70 Gy; normal organ function; no active autoimmunity. During the phase I portion, eligible patients were treated according to treatment-escalation schema following the modified 3+3 design (Table 1). The maximum tolerated combination (MTC) will be the regimen at which ≤ 1/6 patients experience dose-limiting toxicity (DLT) within 8 weeks of the start of study therapy. During the phase II portion, a total of 24 evaluable patients will be enrolled at the MTC using Simon’s MiniMax two-stage design. The primary endpoint of the phase I portion is to determine the MTC. Objective radiological responses (ORRs) are defined as per the Macdonald criteria. One cycle of immunotherapy is defined as 4 weeks of nivolumab with or without concurrent ipilimumab. Results: From 7/2019 to 3/2021, 13 patients were enrolled in the phase I, including 6 with regimen A and 7 with regimen B (Table). The median prior RT dose was 56 Gy (18-70) at a median interval of 2.8 years (1.3-13.3). There was no DLT in either cohort, so regimen B was deemed the MTC. The median cycles of immunotherapy completed were not significantly different between cohort A and B (11 vs. 6, p = 0.41, respectively). Three cohort A patients and 2 cohort B patients completed all planned doses of immunotherapy. Most patients stopped due to progression, and only one cohort B patient stopped due to treatment-related toxicity (grade 3 hypophysitis and encephalitis after 6 cycles of immunotherapy). After a median follow-up of 11.1 months, there have been 5 progressions and 4 deaths. The 6 month-PFS and 12 month-PFS rates are 62% and 54%, respectively. Two ORRs have been reported by institutional assessment, and central radiology review is ongoing and will be reported. Conclusions: Reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab are well tolerated for radiation-relapsed high-grade meningiomas. Phase II study of regimen B is currently enrolling. Clinical trial information: NCT03604978. [Table: see text]
A multicenter, randomized, double-blind, phase III trial comparing denosumab biosimilar QL1206 and denosumab in patients with bone metastases from solid tumors.
Authors: Li Huiping , Huang Yan , Zhang Li , Chen Zhendong , Zeng Aiping , Zhang Helong , Yu Yan , Wei Shihong , Li Qingshan , Wang Xiaojia , Wang Xiangcai , Wang Xiuwen , Yang Runxiang , Dai Xiumei , Bi Minghong , Sun Tao , Zhang Qingyuan , Han Cuicui , Liu Qianqian , Li Yujie 
Published: June 2022

2526 Background: This phase III study compared clinical efficacy, safety of the first biosimilar QL1206 with denosumab in solid tumor patients with bone metastases. Methods: Patients aged 18-80 years, with bone metastatic solid tumors and ECOG performance status of 0-2 were randomly assigned 1:1 to receive subcutaneous QL1206 or denosumab (120 mg Q4W, both) based on stratification factors (tumor types, previous skeletal-related event [SRE], and current systemic anti-tumor therapy). The primary efficacy endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide/creatinine ratio (uNTX/uCr); Clinical equivalence would be confirmed if the two-sided 90% confidence intervals (CI) of the least-squares mean (LSM) difference of natural log-transformed ratio of week 13 uNTX/uCr to baseline calculated by analysis of covariance were within the margins of ±0.135. The secondary endpoints included the percentage changes from baseline to week 25 and 53 in uNTX/uCr, the percentage changes from baseline to week 13, 25 and 53 in serum bone-specific alkaline phosphatase (s-BALP) and the time to on-study SRE. Adverse events (AE), immunogenicity (IG) and pharmacokinetics (PK) were also assessed. Population PK was analyzed using nonlinear mixed effects model. Results: 717 patients were randomized to the QL1206 (n = 357) and denosumab (n = 360) groups, respectively. The median percentage changes at week 13 in uNTX/uCr were -75.2% for QL1206 and -75.8% for denosumab. LSM of natural log-transformed ratio of week 13 uNTX/uCr to baseline were -1.429 (standard error 0.130) and -1.441 (0.130) in the two groups. The LSM difference between the two groups was 0.012 (90% CI -0.078 to 0.103; P = 0.8208), within the equivalence margins. Analyses for subgroups of sex, age, and randomization strata showed almost no significant differences. The secondary endpoints were also similar between the two groups (median percentage changes in s-BALP from baseline to week 13: -38.0% vs -37.1%; hazard ratio of time to SRE: 1.264 [95% CI 0.670 to 2.383]; both P > 0.05). In the safety set, treatment-emergent AE occurred in 332 of 356 patients (93.3%) in the QL1206 group and 348 of 361 (96.4%) in the denosumab group. The proportions of positive anti-drug antibody (14/345 [4.1%] vs 16/352 [4.5%]), neutralizing antibody (three [0.9%], each), and PK characteristics were similar between the two groups. Conclusions: The results suggest that QL1206, the first biosimilar denosumab, is similar to denosumab with respect to clinical efficacy, acceptable safety, IG, and PK characteristics. The totality of evidence supports clinical equivalence of QL1206 and denosumab. Clinical trial information: NCT04550949.
Novel platform for identifying multiple cancer-specific antigens.
Authors: Mor Danielle , Farooqui Shakeel , Manavalan John , Davis Joseph , Davis Elliot 
Published: June 2022

2530 Background: Virtually all cancer treatments that kill cancer cells also adversely affect normal cells and often have debilitating side effects. A key challenge has been to identify antigens that are suitable for antibody-based targeted therapeutics. We have developed a novel platform to detect and identify multiple cell surface antigens that are unique to human cancers. Methods: Breast Cancer cells (Hs578T) or Melanoma cells (Hs895.T) were injected into rabbits to generate polyclonal xeno-antibodies. The resulting serum against each cancer was then incubated with normal cells of the same tissue type derived from the same patients; Breast Epithelium (matched-pair Hs578Bst) or Skin Fibroblasts (matched-pair Hs895.Sk) in order to absorb antibodies that cross-react with antigens on normal tissue (U.S. Patent Application No. 16/243,161). Flow cytometry was used for measuring the binding capacity of the unfiltered serum and filtered serum (lacking cross-reacting antibodies) on both the cancer cells and normal cells. Cytotoxicity assays were performed using a secondary ADC (anti-rabbit IgG specific antibody conjugated to MMAF), to determine the cytotoxicity of the unfiltered antibodies and filtered antibodies on normal and cancer cells. Results: Flow cytometry revealed, for antibodies against breast cancer, there was 90.3% and 88.6% binding to breast cancer cells and normal breast epithelial cells, respectively, pre-filtration; and 78.9% and 23% binding, respectively, post-filtration. For antibodies against melanoma, there was 89.2% and 86.6% binding to melanoma cells and normal skin fibroblasts, respectively, pre-filtration; and 55.1% and 0% binding, respectively, post-filtration. The Table summarizes the cytotoxicity of unfiltered and filtered antibodies on cancer cells and normal cells. Remarkably, there was preferential killing of all the cancer cells tested by both unfiltered and filtered antibodies, while there was no cytotoxicity in the normal cells using filtered antibodies. Cytotoxicity was also observed when antibodies generated against one type of cancer were incubated with other cancer types. Conclusions: This data suggests that our xeno-antibody based method can detect cancer-specific sites, not found on normal cells, and diverse cancer types may share a common antigenic signature. These findings are significant for identifying unique antigens on cancer cells and designing targeted therapies against cancer. [Table: see text]
Multicenter phase Ib trial in the U.S. of salvage CT041 CLDN18.2-specific chimeric antigen receptor T-cell therapy for patients with advanced gastric and pancreatic adenocarcinoma.
Authors: Botta Gregory P. , Becerra Carlos Roberto , Jin Zhaohui , Kim Dae Won , Zhao Dan , Lenz Heinz-Josef , Ma Hong , Ween Audrey , Acha Petra , Li Zonghai , Yoon Harry H. 
Published: June 2022

2538 Background: Claudin 18.2 (CLDN18.2) is a highly selective cell lineage marker with limited expression in normal gastric tissues and significantly higher expression in primary gastric, pancreatic tumors and their metastases. Anti-CLDN18.2-targeted CAR T cells, termed CT041, were developed to evaluate tumor response and patient-reported outcomes in the gastric and pancreatic cancer. Preliminary results of the trial (NCT03874897) showed an objective response rate (ORR) of about 60% in gastric cancer from a non-Western population. Here we report the results of CT041 for metastatic gastric cancer after ≥ 2 prior lines of systemic therapy or pancreatic cancer ≥ 1 prior line from six centers in the United States. Methods: This single-arm, open-label, phase Ib study (NCT04404595) investigated autologous CT041 CAR T cells in patients with CLDN18.2 positive advanced gastric (including diffuse, signet-ring) or pancreatic adenocarcinoma. All patients completed a conditioning regimen consisting of fludarabine, cyclophosphamide, and nab-paclitaxel prior to CT041 CAR T cells. The primary objective was to assess the safety, efficacy and cytokinetic profile of CT041. Adverse Events (AEs) were graded according to CTCAE 5.0, and tumor response was assessed per RECIST 1.1. Results: As of February 15, 2022, 11 patients (5 gastric and 6 pancreatic) with a median of 2 prior lines of therapy (range 1- 4) were treated with CT041 at a dose between 2.5 and 4 x 108 cells. There were no dose limiting toxicities, treatment-related deaths, severe cytokine release syndrome (CRS), immune effector cell-associated neurologic syndrome (ICANS), or severe gastrointestinal (GI) related AEs. All CRS were grade 1 or 2. Only one patient received tocilizumab. No grade 4 AEs were observed except for hematologic toxicities related to conditioning. The first eight patients were evaluable for response by the date of data cut-off: 1 patient achieved a complete response after two CT041 doses (gastric), 2 had partial response (gastric), 2 had stable disease with tumor shrinkage (pancreatic) and 3 (pancreatic) had progression of disease after an initial biochemical response. ORR was 37.5% (3/8) in all patients including 100% (3/3) in the gastric subgroup (all ≥ 3 prior lines). The last three patients had not reached the time for response assessment. CAR T cell expansion correlated with ctDNA reduction. The median duration of response and the progression-free survival had not been reached. Conclusions: These preliminary results indicate that CT041 therapy was safe and had therapeutic efficacy in patients with advanced GI cancers. In heavily pre-treated gastric cancer, CT041 may have significantly improved anti-tumor activity compared to historical treatment regimens. Clinical trial information: NCT04404595.