bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teleoncology: Assessing online communication skills of millennial medical students.
Authors: Gil Deza Ernesto , Gil Deza Lourdes , Abal Mariana , Dragosky Marta , Acuna Claudia Lorena , Marin Ordoñez Alba , Montiel Monica , Tognelli Flavio A , Smolje Leonel , Gonzalez Cesar , Brandon Maximiliano , Garcia Gerardi Carlos , Martin Reinas Gaston , Ares Sandra L. , Gercovich Daniela , Rivarola Edgardo G. J. , Morgenfeld Eduardo L. , Gercovich Felipe G. ,   IOHM-USAL-ECOE 2020
Published: June 2021

e13616 Background: COVID-19 posed new challenges in patient care and led to an increase in teleoncology. This paper analyzes telemedicine communication skills of millennial medical students of the postgraduate program of Clinical Oncology at Universidad del Salvador, Buenos Aires. Methods: Student assessment was based on a video call interaction with simulated patients in two stations (30 minutes each) of the Virtual Observational Standard Clinical Examination (V-OSCE), implemented in November 2020. Students received virtual communication guidelines and participated in training sessions to use the video call platform. All interactions were recorded. Assessment items (Table). Results: A total of 25 students were evaluated: 1 (4%) was ineligible due to network connection issues; 24 (96%) participated in both interactions. We analyzed 48 interactions in total. Opening: 6/48 interactions completed all five required items. Most recurring problems: not checking for patient’s previous experience with teleoncology (37/48) and not providing an alternative communication channel in case of technical difficulties (40/48). Middle: the results were similar to in-person interaction observed in previous exams, 35/48 interactions completed all required items. End: 16/48 interactions completed both items. In 32/48 the student did not check for patient understanding of the information provided. Only 3/48 interactions completed all 12 items. Conclusions: A) The V-OSCE is a useful tool to practice and evaluate teleoncology communication skills. B) The Middle Moment of the interactions was similar to an in-person interaction. However, the Opening and End of the interview were more challenging. The most critical struggles being: checking for patient’s previous experience in teleoncology, providing an alternative communication channel in case of technical difficulties and checking for patient understanding. C) COVID-19 established new forms of communication that are likely to remain even after the pandemic has ended. It is important to address this demand for online communication skills in medical education curricula.[Table: see text]
A prognostic model based on CGGA and TCGA databases for predicting outcome of glioma patients.
Authors: Ni Hongbin , Zhang Xing , Wang Xiaoxuan , Song Chao 
Published: June 2021

e14017 Background: Glioma is the most frequent primary malignance of the central nervous system (CNS) and causes the top-ten deaths of cancers. Isocitrate dehydrogenase ( IDH) mutations and chromosome 1p and 19q codeletion are the known prognostic factors of glioma. However, it is still not enough to predict the outcomes. Herein, we conduct a prognostic model of patients with gliomas. Methods: The Chinese Glioma Genome Atlas (CGGA) contained 286 patients with whole-exome sequencing (WES) was used to established the model. Kaplan-Meier analysis based on log-rank test was used to confirm the single mutation overall survival (OS) factors (allele frequency≥ 5) in CGGA. The model was established based on the Cox regression of above significant factors. The data of 1122 patients with glioma in TCGA (The Cancer Genome Atlas) was used to validate the model. Results: According to the CGGA database, the OS factors of glioma patients were 1p/19q, CIC, EGFR ( p< 0.001), IDH1, IRS2, NF1, NOTCH1, PDGFRA, PTEN, ROS1, SMARCA4 and TP53. The Cox regression revealed 1p/19q codeletion (HR = 2.008, 95%CI 1.397-2.885, p< 0.001), EGFR (HR = 0.420, 95%CI 0.217-0.811, p= 0.010), PDGFRA (HR = 0.271, 95%CI 0.139-0.528, p< 0.001), and ROS1 (HR = 0.197, 95%CI 0.071-0.549, p= 0.002). Based on the β value of the regression equation, we divided the glioma patients into 3 groups (G1: harboring EGFR, PDGFR and/or ROS1 mutations; G2: wide type; G3: harboring 1p/19q without mutations in three genes). In TCGA, the OS of glioma patients was also showed G1 < G2 < G3 significantly. Conclusions: The prognostic model was divided glioma patients into three groups reasonably and could provide new reference for the glioma management. It needed to be further verified in more cohorts.
Measurement of treatment dependent glioblastoma cell density in T1- weighted contrast enhancement at autopsy.
Authors: Lowman Allison , Bobholz Samuel , Connelly Jennifer Marie , Cochran Elizabeth , Mueller Wade , Brehler Michael , Kyereme Fitzgerald , Sherman John , Duenweg Savannah , LaViolette Peter S 
Published: June 2021

e14035 Background: With an average overall survival of 12-18 months, glioblastoma has a particularly grim diagnosis. Standard treatment of glioblastoma, following detection on MRI, is surgical resection followed by radiation therapy and chemotherapy and is monitored through MR imaging. Glioblastoma has a unique heterogenous nature that complicates visualization of subtly enhancing tumor. This study used autopsy tissue samples taken from glioblastoma patients with varying treatment, to examine the effects of treatment on cell density within regions of contrast enhancement, using T1-weighted subtraction maps (T1S) from the last MR images to death. Methods: Eight patients diagnosed with glioblastoma at autopsy were recruited for this study. Two patients had no treatment and six received a combination of chemo-radiation and other treatments, including but not limited to bevacizumab (Bev) and TTFields therapy. At autopsy, whole brain samples were sliced axially aligned to the patient’s final MRI to death. Time between last MRI and death ranged from 4-27 days (mean 16 days). Overall survival (OS) ranged from 4-538 days (mean 307 days). Large tissue samples were taken from regions of suspected tumor or treatment effect, for a total of 18 tissue samples. Tissue samples were processed, H&E stained, and digitized at 40X resolution (Huron Slide Scanner). Cell density (cells/mm2) was calculated using digital histology. T1S were created for each patient by subtracting intensity normalized T1 weighted images from T1 post contrast images (T1C). Digital histology was aligned and resampled into MRI space using manual control point registration. Mixed effect models were used to compare differences in cell density across contrast enhancement (T1SE vs. NE) as well as across treatment groups (treatment vs. no treatment). Results: Cellularity was compared across regions of T1S enhancement (T1SE) and non-enhancement (NE) within manually selected regions of interest. Cell density compared between regions of T1SE and NE was not different (p=0.219). Total cell density was increased in patients who had received treatment compared to no treatment in both regions of T1SE and NE (p=0.014). Conclusions: Overall, cell density was increased in patients who had received treatment after diagnosis of glioblastoma. Additional research is needed to examine the extent of treatment’s effect on cellularity of glioblastoma. This work begins to characterize the use of T1S in evaluating glioblastoma tumor burden in patients with varying treatment histories.[Table: see text]
High-grade glioma of central nervous system: Single center treatment experience.
Authors: Olgun Nur , Kızmazoğlu Deniz , Özdoğar Batuhan , Çeçen Emre , Kızmazoğlu Ceren , Akyol Sefika , Demiral Ayşe , Çetingöz Rıza , Önal Ayşe , Uçar Handan Güleryüz , Özer Erdener , İnce Dilek 
Published: June 2021

e14040 Background: To evaluate characteristics and treatment responses of patients with high grade gliomas (HGG) in our center Methods: Medical files of patients with malignant CNS tumors between 1987-2020 were analyzed retrospectively. There were 44 patients with HGG. Results: Diagnosis of patients as follows: 21 pons glioma, 2 anaplastic astrocytoma, 11 anaplastic ependimoma, 7 glioblastoma multiforme, 1 glioblastoma, 2 gliomatosis cerebri. The median age at diagnosis was 6,5 yrs (7 – 17 yrs), M/F:25/19. Age distrubution: <5 yrs 12 patients, 5-10 yrs 18 patients, 10-18 yrs 14 patients. The most frequent complaints for pons gliomas: cranial nerve paralysis (52%), visial impairment (48%), headache (38%), power loss (43%) and speech disorder (30%). Surgery was performed to extrinsic component of mass in 3 patients of pons gliomas. For other HGG: 7 subtotal resection and 16 gross total resection had performed. Seven patients died before RT. And other 37 patients received radiotherapy. RT total doses varied between 50-60 Gy. Seven patients were not received chemotherapy, 3 of them died before chemo, and others received only RT. Chemotherapy protocoles were changed over the years: For pons gliomas, MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, only ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and temo + bevacizumab in one patient. Last 3 patients received nimotuzumab-vinorelbine after ICE and temo. For other HGGs, platin based regimens used fort he first line treatment. Temozolamide-bevacizumab, irinotecan-temsirolimus combinations were the other options as second and also third line treatments. Median progression free survival time was 6 mos (2 weeks -25 mos) for pons gliomas, for other gliomas median progression free survival time was 14 mos (0 -74 mos). For pons gliomas: Event free survival rate for 6 mos was 75%, for one year was 17%, One year, 18 mos, and two years overall survival rates were 84%, 52% and 10% respectively. For other HGGs: Event free survival rate for one year and two years were 57% and 17% respectively. One year and two years overall survival rates were 73% and 36% respectively. Conclusions: High grade glioma is a group of tumor in which still the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, prognosis is very poor. The progression free and overall survival rates of patients were similar to literature. With new developments in molecular pathology, as the use of molecular target therapies, the progression free survival rates newly will improve.
Optic glioma in children: Turkish experience.
Authors: Yaman Bajin Inci , Korones David Nathan , Aydin Burca , Karli Oguz Kader , Kurucu Nilgun , Yalcin Bilgehan , Varan Ali , Kutluk Tezer 
Published: June 2021

e14042 Background: Optic gliomas are the most common tumors of the optic pathway, comprising about 1% of all intracranial tumours. Here we present the clinical characteristics and the outcome of patients with optic glioma at our institution. Methods: Seventy two patients diagnosed and followed up at a pediatric cancer center in Ankara, Turkey between January 1, 2008 and December 31, 2020 were included in this analysis. The clinical features and outcome of patients were recorded from patient files and hospital information system retrospectively. Results: The median age at the time of diagnosis was 3.5 years (4-157 months), the female/male ratio was 1.3. Fourteen children (19%) were asymptomatic and tumors were detected with routine surveillance, and 58 (81%) had symptoms (the most common being proptosis in 16 patients (22%)). The most common site of optic glioma was the intraorbital region (31%). Fourty patients (55%) had neurofibromatosis type 1 (NF-1). Five patients had histopathological diagnoses; 3 pilomyxoid astrocytoma, 2 pilocytic astrocytoma. Children were treated if they had tumor progression on MRI and/or worsening visual acuity. Twenty seven (38%) children were observed without any therapy, 6 patients (8%) received radiation and chemotherapy, 4 patients (5%) received radiation only, and 35 patients (49%) received chemotherapy only. Treatment regimens for the 41 children who received chemotherapy included carboplatin/etoposide (17), cisplatin/etoposide (18), carboplatin/vincristine (5), and temozolomide (1). The 5-year progression-free survival (PFS) and overall survival (OS) were 64% and 90%, respectively with a 31 month median follow-up. The 5 year PFS was significantly lower in patients with optic tract-hypothalamic-chiasmatic involvement (34%) than orbital involvement (83%) (p=0.013). Five year PFS was significantly higher in patients with NF-1 (80%) than patients without NF-1(46%) (p=0.027) and significantly lower in patients diagnosed at <3 years old (37%) (p=0.05). Five patients died of disease, and one died of infection after chemotherapy. Two patients treated with platin (1 carboplatin, 1 cisplatin) developed ototoxicity. One patient with NF-1 developed Moya-Moya disease. Two patients developed multiple pituitary hormone deficiencies and one patient developed precocious puberty during follow-up. No secondary malignancy was observed. Conclusions: The management of optic glioma remains challenging. Although the overall survival for children with this disease is excellent, progression of disease is frequent, particularly in those children without NF-1, younger children and non-orbital tumors. This study from Turkey showed comparable results with high-income countries. Further studies with longer follow-up periods are needed to find appropriate treatment strategies.
The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.
Authors: Ding Xingchen , Yu Jinming , Hu Man 
Published: June 2021

e14043 Background: Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it also increases PD-L1 expression in intracranial tumor is still unknown. Here we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. Methods: Tumor tissues from 120 patients with glioma, were analyzed for PD-L1 and HIF-1α expression using immunohistochemistry. And results were verified in vitro, using U251, U343 glioma cell lines. Gene expression were evaluated by quantitative PCR; protein levels were analyzed by Western blot; ChIP-qPCR (chromatin immunoprecipitation coupled with quantitative PCR) analysis showed the relationship between HIF-1α and PD-L1. Glioma in situ model were used to explore whether HIF-1α inhibitor (PX-478) can enhance anti-PD-L1 therapy responses. Tumor volume was measured twice weekly. Immune data were further analyzed by FACS DIVA 7.0 or Flow Jo 7.6.5 software. Results: In glioma patients, HIF-1α and PD-L1 were markedly overexpressed in high grade glioma (HGG) tissues and were both associated with poorer overall survival(OS) (PD-L1( < 5% vs. ≥ 5%): 3, 5, 10-year OS: 78.1%, 50.5%, 27.2% vs. 45.4%, 11.8%, 0%, P = 0.0026; HIF-1α( < 1% vs. ≥ 1%): 3, 5, 10-year OS:74.2%, 66.8%, 53.4% vs. 61.6%, 21.0%, 0%, P = 0.001). And the expression of PD-L1 was significantly positively correlated with the expression of HIF-1α in glioma patients ( r = 0.412, P < 0.001). In glioma cell lines, PD-L1 expression was significantly induced under hypoxia condition, but the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter, providing evidence that HIF-1α up-regulate PD-L1 expression in glioma cells. In glioma murine model, combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to mice treated with either single agent. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Conclusions: Multiple findings demonstrated that positive relationship between HIF-1α and PD-L1 existed in glioma cells under hypoxia condition. These observations also provide invaluable information that hypoxia contributes to a key phase of glioma cells evading adaptive immunity, thereby promoting malignant progression and poorer clinical outcomes. Given these, it would be a potential strategy to target HIF-1α in combination with the blockage of PD-1/PD-L1 pathway for anti-cancer in the future.
Landscape of hyper-progression related gene alterations among Chinese population and their impact on patients’ survival after immunotherapy.
Authors: Fu Wenfan , Li Si , Xi Wenjing , Yang Qidong , Chen Dongsheng , Xiao Mingzhe 
Published: June 2021

e14518 Background: Immune checkpoint inhibitors (ICIs) have demonstrated salutary anticancer effects in patient with cancer. However, more than 10% of treated patients had experienced hyper-progressive disease (HPD), which resulted poor survival. Gene alterations might be associated with HPD, while more studies are needed to clarify their impact on survival and role in tumor progression. Methods: In this analysis, we retrospectively reviewed genomic alterations in 1814 Chinese patients with cancer of lung, liver, colorectal, gastric, pancreatic, biliary duct, melanoma, cervical and esophagus. Next-Generation Sequencing (NGS) by a customized 539-gene panel was performed. Frequency of HPD gene alterations, including amplification of MDM2/4, CCND1 and FGFR3/4, loss of CDKN2A/B, mutations in DNMT3A were investigated. Their impact on progress-free survival (PFS) after immunotherapy were further explored in lung cancer in Rizvi et. 2018 cohort. Results: Of 1814 patients, 449 (24.8%) harbored at least 1 HPD related gene alterations. Esophagus cancer (7/12,58.3%), melanoma (10/23, 43.5%) and liver cancer (108/268, 40.3%) took the largest proportion. The frequencies for each gene were CDKN2A loss (8.5%), CDKN2B loss (8.1%), DNMT3A mutation (7.8%), MDM2 amp (4.9%), MDM4 amp (3.8%), CCND1 amp (3.2%), FGFR4 amp (0.6%), FGFR3 amp (0.3%), respectively. Significant higher TMB in altered group was revealed in EGFR/ALK negative lung cancer (5.88 mut/Mb vs. 2.84 mut/Mb (wild group), P= 0.001). In Rivzi et. 2018 cohort, 46/240 (19.2%) patients had related gene alterations. The TMB was comparable between altered and wild-type groups. Median PFS were 2.5 months and 3.8 months for altered and wild-type group ( P= 0.074). Among altered patients, 17.4% achieved PFS > 6 months (Table 1), two of them had a 1-year PFS (1 with CDKN2A&B loss, 1 with DNMT3A). Conclusions: A considerable proportion of patients harbored HPD related gene alterations. Although they tend to present poorer PFS, there’re patients had the PFS>12 months, the exact impact and underline mechanisms requires more evidence. Distribution of progression-free survival (PFS) for each gene.[Table: see text]
Frequency of minimal residual disease as measured by ctDNA in mismatch repair deficient tumors following curative resection.
Authors: Lumish Melissa Amy , Jayakumaran Gowtham , Fox Maggie , Sabwa Shalom , Cercek Andrea , Stadler Zsofia Kinga , Ku Geoffrey Yuyat , Segal Neil Howard , Won Elizabeth , Maron Steven Brad , Troso-Sandoval Tiffany A. , Segal Michal Fani , Strong Vivian E. , Molena Daniela , Weiser Martin R. , Jones David Randolph , Zehir Ahmet , Berger Michael F. , Diaz Luis A. , Janjigian Yelena Y. 
Published: June 2021

e14520 Background: Mismatch repair deficient (MMRd) tumors are highly sensitive to checkpoint blockade (CPB) in patients with metastatic disease regardless of tumor type. However, the efficacy of CPB in the adjuvant setting is unknown, especially since MMRd is considered a favorable biomarker for most resected tumor types. Circulating tumor DNA (ctDNA) could be used to screen for patients at high risk for recurrence following surgery or adjuvant chemotherapy and identify patients (pts) that would most benefit from CPB. Methods: To assess the frequency of ctDNA in the resected MMRd population, we prospectively screened pts with MMRd tumors who completed standard perioperative chemotherapy and surgery (NCT03832569). DNA from resected tumors and matched postoperative plasma was sequenced for the presence of somatic mutations. Patients were considered to have minimal residual disease (MRD) when mutations were identified in tumor and found to be identical to those in matched plasma DNA. Somatic tissue mutations were assessed using MSK-IMPACT and ctDNA was assessed using FoundationOne, Guardant360 or MSK-ACCESS. Results: A total of 86 pts were screened for the presence of MRD. These represented 7 tumor types with colorectal (63%), endometrial (16%) and esophagogastric (13%) being the most common. The majority of pts were stage III (49%). MRD was detected in 18% of cases (14 of 79). Among the MRD negative group (n=62), only one pt developed disease recurrence. Three samples failed ctDNA analysis for technical reasons. Conclusions: MRD was identified in 18% of resected MMRd tumors using ctDNA analysis, suggesting this to be a feasible tumor agnostic approach to test the efficacy of CPB in a pts at high-risk for recurrence. Future studies will assess the impact of CPB in MRD positive MMRd tumors.[Table: see text]
Artificial intelligence-powered spatial analysis of tumor infiltrating lymphocytes (TIL) to reflect target gene expressions of novel immuno-oncology agents.
Authors: Ock Chan-Young , Shin Seunghwan , Jung Wonkyung , Ahn Sangheon , Kim Haejoon , Lee Chunggi , Aum Jaehong , Tak Daim , Ryu Ahyoung , Chung Taiwon , Baek Eunji , Shin Jisoo , Lee Seungje , Shin Jiwon , Ma Minuk , Park Seonwook , Pereira Sergio , Kang Jeongseok , Yoo Donggeun , Paeng Kyunghyun 
Published: June 2021

e14534 Background: Novel immuno-oncology (IO) agents are promising but showing their efficacy in early phase clinical trials has been challenging due to limited enrichment strategies using practical biomarker platforms. We hypothesize that an artificial intelligence (AI)-powered spatial analysis of TIL using practically feasible H&E slides, can reflect a specific target gene expression derived from RNA sequencing. This enhances its potential application in early development of novel IO agents. Methods: An AI-powered spatial TIL analyzer, namely Lunit SCOPE IO, was developed with data from 2.8 x 109 micrometer2 H&E-stained tissue regions and 5.9 x 106 TILs from 3,166 whole slide images of multiple cancer types, annotated by board-certified pathologists. Inflamed Score and Immune-Excluded Score was defined as the proportion of all tumor-containing 1 mm2-size tiles within a WSI classified as being of inflamed immune phenotype (high TIL density within cancer epithelium) and immune-excluded phenotype (low TIL density within cancer epithelium, but high TIL density within stroma), respectively. We used RNA sequencing data and H&E images from The Cancer Genome Atlas database, excluding those of mesenchymal origin (n = 7,467). Spearman's rank correlation between each gene expression and IS or IES, respectively, was calculated. Correlation coefficient > 0.2 and false discovery rate (FDR) < 1% was considered as a significant correlation. Results: In a total of 20,304 genes, 871 (4.3%) and 1,155 (5.7%) genes were significantly correlated with Inflamed Score (IS) and Immune-Excluded Score (IES), respectively. The IS was highly related to genes reflecting immune cytolytic activity and targets of approved immune checkpoint inhibitors (Table). Interestingly, it was also significantly correlated with target genes of novel IO such as TIGIT, LAG3, TIM3, IDO, Adenosine receptor A2A, OX40, ICOS, M-CSF, IL2, IL7, and IL12. Moreover, the IES was exclusively correlated with the target genes of CEACAM, TGFB, and IL1. Conclusions: Expression levels of novel I-O target genes are correlated with three scores derived from AI-powered TIL analysis using H&E slides, which can be easily applied to clinical research.[Table: see text]